• 생명과학회지
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• 제11권2호
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• pp.181-189
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• 2001

Cytokines are hormone-like proteins which mediate and regulast inflammatory and immune responses. Transforming growth factor -$\beta$1(TGF-$\beta$) plays an important role in the control of the immune response and wound healing, and in the development o various tissues and organs, Nitric oxide(NO) is major messenger molecule regulating immune function and blood vessel dilation and serving as a neurotransmitter in the brain and peripheral nervous system. Also, NO is to be a potent mutagen that cause mutation in the p53 tumor suppressor gene in early phases of human gastric carcinogenesis. The purpose of this study was to investigate the effect of Helicobacter phlori lystes, lipopolysaccharide (LPS), and Staphylococcus enterotoxin B(SEB) on production of TGF-$\beta$1 and NO by human fibroblasts. Primary cultured human fibroblasts were incubated with H. pylori lysates(Hp), LPs, SEB, Hp+LPS, Hp+SEB, Hp+LPS+SEB. Cultured supernatants that were collected at 24, 48 and 72 hr were assessed for TGF-$\beta$1 by enzyme-linked immunosorbent assay and NO production by quantification of nitrite ion. TGF-$\beta$1 production in fibroblasts exposed with Hp, LPS or SEB for 48 hrs was enhanced, but for 72 hrs inhibited. Its production by doble exposure such as Hp+LPS, Hp+SEB, Hp+LPS+SEB was lowered in comparison with single exposure of Hp in cases of 24 and 48 hrs incubation, but for 72 hrs decreased in Hp vaculoating toxin(+), increased in Hp vacuolating toxin(-). No production in fibroblasts increaed at all doses of LPS. But its production by exposure of SEB increased or decreased according to dose and incubation time. Also, NO production by Hp vacuolating toxin(+) increased at all doses, but its production by Hp vacuolating toxin(-) decreased. Its production by doble exposure such as Hp+LPS, Hp+SEB, Hp+LPS+SEB decreased in comparison with single exposure Hp Therefore, quantities pf TGB-$\beta$1 and NO released by human fibroblasts shows differences according to kinds of stimulants. Also, in care stimulated with same kinds of stimulants, its productions exhibit quantitative differences according to exposure times. These results suggest that the decreased of TGF-$\beta$1 in fibroblasts by mixed exposure with Hp producing vacuolating toxin and bacterial toxins such as LPS and SEB may effect negatively in healing of host tissue and increased of NO by infection oh H. pylori may related to the increased susceptibility for human gastric carcinogenesis.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6139-6144
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• 2012

Aims: Mammalian target of rapamycin (mTOR) is master regulator of the PI3K/Akt/mTOR pathway and plays an important role in NSCLCs. Here we characterized mRNA and protein expression levels of mTOR and its functional associated molecules including PTEN, IGF-1R and 4EBP1 in surgically resected NSCLCs. Methods: Fifty-four patients with NSCLCs who underwent pulmonary resection were included in current study. mRNA levels of mTOR, PTEN, IGF-1R, and 4EBP1 were evaluated by RT-PCR and protein expression of mTOR, PTEN, and IGF-1R by immunohistochemistry (IHC). Association of expression of the relevant molecules with clinical characteristics, as well as correlations between mTOR and PTEN, 4EBP1 and IGF-1R were also assessed. Results: The results of RT-PCR showed that in NSCLCs, the expression level of mTOR increased, while PTEN, 4EBP1 and IGF-1R decreased. Statistical analysis indicated high IGF-1R expression was correlated with advanced clinical stage (stage III) and PTEN expression was reversely associated with tumor size (P=0.16). The results of IHC showed mTOR positive staining in 51.8% of cases, while IGF-1R positive staining was found in 83.3% and loss of PTEN in 46.3%. Protein expression of mTOR was correlated with its regulators, PTEN and IGF-1R, to some extent. Conclusions: Abnormal activation of mTOR signaling, high expression of IGF-1R, and loss of PTEN were observed in resected NSCLC specimens. The poor expression agreement of mTOR with its regulators, PTEN, and IGF-1R, implied that combination strategy of mTOR inhibitors with other targets hold significant potential for NSCLC treatment.

• Asian Pacific Journal of Cancer Prevention
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• 제17권9호
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• pp.4247-4250
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• 2016

Background: Pax8 and peroxisome proliferator-activated receptor gamma 1 gene (Pax8-$PPAR{\gamma}1$) are important factors in tumors. Several studies have suggested that follicular thyroid cancer may arise from Pax8- $PPAR{\gamma}1$ rearrangement. In order to have a better understanding of the association between Pax8-$PPAR{\gamma}1$ rearrangement and follicular thyroid cancer, we conducted the presenmt meta-analysis. Materials and Methods: The information was extracted from PubMed, EMBASE and Web of Science. Statistic analysis was performed with Stata12.0 software. Odds ratios (ORs) were calculated using a fixed-effects model. We also performed heterogeneity and publication bias analyses. Results: Nine studies including 198 follicular thyroid cancer patients and 268 controls were considered eligible. The frequency of Pax8-$PPAR{\gamma}1$ rearrangement was significantly higher in the follicular thyroid cancer group than in the control group, with a pooled OR of 6.63 (95%CI=3.50-12.7). In addition, through subgroup analysis, the OR between Pax8-$PPAR{\gamma}1$ rearrangement and follicular thyroid cancer was 6.04 (95%CI = 3.18-11.5) when using benign tumor tissues as controls. The OR for the method subgroup was 9.99 (95% CI =4.86-20.5) in the RT-PCR. Conclusions: The final results demonstrated that Pax8-$PPAR{\gamma}1$ rearrangement has significant association with follicular thyroid cancer.

• 식물병연구
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• 제12권3호
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• pp.189-196
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• 2006

2003년 대전광역시 유성구에서 벤자민고무나무의 줄기에 뿌리혹병이 발생하였다. 혹은 15cm정도의 크기로 표면이 거칠고 갈변된 타원형이었다. 혹 조직으로부터 Agrobacterium과 유사한 세균을 분리하였으며 벤자민고무나무의 유묘에 접종하여 혹을 형성한 5개 균주 중에서 2가지 계통에 대하여 분류학적 특성을 조사하였다. 0.5% $CaCO_3$가 첨가된 PDA 배지에서 생장된 병원성 세균들은 둥글고 볼록하면서 광택이 나는 크림색 계통이었다. 모든 균주는 다수의 편모를 가진 간상의 세균으로 그람음성이었으며 호기적으로 생장하면서 D1M agar에서도 생장하였다. 병원성 세균들은 대조균주와 상이한 특성을 가지고 있었으나 주요 생리 생화학적특성, 탄소원 이용양상, 지방산조성 분석 결과에 근거하여 A. larrymoorei와 A. tumefacien로 동정되었다. A. larrymoorei와 A. tumefaciens는 포도를 제외한 타 기주식물에서도 병원성이 있었다. 국내에서 A. larrymoorei와 A. tumefaciens에 의한 벤자민고무나무의 뿌리혹병은 본 연구에서 처음 보고된다.

• 식물병연구
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• 제12권3호
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• pp.197-204
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• 2006

2001년 경기도 화성시와 2004년 경상북도 구미시에서 국화의 줄기와 뿌리에 뿌리혹병이 발생하였다. 혹의 모양과 색은 상이하였으나 표면이 거칠고 갈변된 타원형이었다. 혹 조직으로부터 분리한 20개 균주 중 국화의 유묘에 접종하여 혹을 형성한 9개 균주에 대하여 분류학적 특성을 조사하였다. 0.5% $CaCO_3$가 첨가된 PDA배지에서 생장된 콜로니들은 둥글고 볼록하면서 광택이 나는 크림색이었다. 모든 균주는 다수의 편모를 가진 간상의 세균으로 그람음성이면서 호기적으로 생장하였으며 D1M agar 에서도 생장하였다. 병원성 세균들은 대조균주와 상이한 특성을 가지고 있었으나 주요 생리 생화학적특성, 탄소원 이용양상, 지방산조성 비교 결과에 근거하여 8개 균주는 Agrobacterium tumefaciens로 1개 균주는 A. rubi로 동정되었다. A. tumefaciens 계통들은 A. rubi 계통보다 병원성이 강하였으며 기주범위가 넓었다. 국내에서 A. tumefaciens와 A. rubi에 의한 국화의 뿌리혹병은 본 연구에서 처음 보고되는 것이며 자연상태에서 A. rubi에 의해 국화의 뿌리혹병이 발생된 사례는 전 세계적으로 처음이다.

• 동의생리병리학회지
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• 제20권2호
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• pp.383-387
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• 2006

To investigate the effect of GyeongshinhaeGihwan 1(GGT1) frequently used as an anti-obesity herbal medicine in oriental medicine on the expression of obesity-related genes, we measured the changes in mRNA levels of these genes by GGT1 in human growth hormone transgenic (hGHTg) obese female rats, and these effects by GGT1 were compared with those of reductil (RD), an anti-obesity drug approved by FDA. Rats received once daily oral administrations of autoclaved water, RD, or GGT1 for 8 weeks. At the end of study, rats were sacrificed and tissues were harvested. Total RNA from adipose tissue, liver and kidney was prepared and the mRNA levels for LPL (lipoprotein lipase), $PPAR{\gamma}$ (peroxisome proliferator activated receptor-gamma), $PPAR{\delta}$ (peroxisome proliferator activated receptor-delta), leptin, $TNF{\alpha}$ (tumor necrosis factor-alpha), and internal standard G3PDH (glyceraldehyde-3-phosphate dehydrogenase) were analyzed by RT-PCR. Compared with control group, $PPAR{\gamma}$ mRNA levels of liver and kidney were decreased in both RD and GGT1 groups, and the effects were more prominent in GGT1 group than in RD group, suggesting that GGT1 is effective in the inhibition of lipid storage by decreasing the $PPAR{\gamma}$ expression. $PPAR{\delta}$ mRNA levels of adipose tissue were increased by RD and GGT1 compared with DW, and the magnitude of increase were higher in GGT1 group than in RD group, indicating that GGT1 stimulates fatty acid oxidation and energy metabolism by activating $PPAR{\delta}$ expression. GGT1 group had higher concentrations of serum leptin, a well-known inhibitor of appetite, than control and RD groups. However, The mRNA levels of leptin, LPL, and $TNF{\alpha}$ were not changed by GGT1. These results indicate that GGT1 can prevent obesity in hGHTg obese female rats by down-regulating and up-regulating the mRNA expression of $PPAR{\gamma}$ and $PPAR{\delta}$, respectively, and that this anti-obesity effects were more pronounced in GGT1 group compared with RD group. In addition, GGT1 seems to inhibit obesity by increasing the circulating leptin levels.

• 한국식품영양과학회지
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• 제43권3호
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• pp.349-354
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• 2014

세포내 $Ca^{{+}{+}}$의 증가는 비만세포에서 수용체 활성을 거치지 않고 탈과립을 유도한다. 괴화는 천연 염색 재료로 사용되고 있으며, 또한 항염증 작용과 $Fc{\varepsilon}RI$와 IgE 가교에 의한 항알레르기 효능도 보고되었다. 이번 연구에서 비만세포에서 $Ca^{{+}{+}}$ 유입에 의해 생산되는 알레르기 매개물에 대한 괴화 추출물의 조절 기능을 보고한다. 괴화 추출물은 A23187에 의해 유도되는 IL-4와 TNF-${\alpha}$의 생산과 탈과립을 저해하였다. 또한 괴화 추출물은 DNFB로 유도한 알레르기 피부염의 동물 모델에서 알레르기 반응을 억제하였다. 괴화추출물 50 mg/kg을 경구투여 또는 도말을 한 경우, DNFB를 단독으로 처리한 군보다 IL-4, TNF 그리고 IFN-${\gamma}$와 같은 염증성 사이토카인의 생산량이 감소하였다. 또한 괴화 추출물을 처리한 경우 혈청 내 IgE의 함량이 DNFB를 단독으로 처리한 군보다 감소하였다. 괴화 추출물을 처리한 군에서의 비장과 림프절의 무게도 DNFB를 단독으로 처리한 군보다 감소하였다. 이러한 결과를 토대로 괴화는 비만세포에서 $Fc{\varepsilon}RI$ 자극뿐만 아니라 $Ca^{{+}{+}}$의 유입에 의한 항알레르기 효능이 있다는 것을 보고한다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6145-6150
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• 2014

Toll-like receptors (TLRs) are expressed in immune and tumor cells and recognize pathogen-associated molecular patterns. Cervical cancer (CC) is directly linked to a persistent infection with high risk human papillomaviruses (HR-HPVs) and could be associated with alteration of TLRs expression. TLR9 plays a key role in the recognition of DNA viruses and better understanding of this signaling pathway in CC could lead to the development of novel immunotherapeutic approaches. The present study was undertaken to determine the level of TLR9 expression in cervical neoplasias from Tunisian women with 53 formalin-fixed and paraffin-embedded specimens, including 22 samples of invasive cervical carcinoma (ICC), 18 of cervical intraepithelial neoplasia (CIN), 7 of condyloma and 6 normal cervical tissues as control cases. Quantification of TLR9 expression was based on scoring four degrees of extent and intensity of immunostaining in squamous epithelial cells. TLR9 expression gradually increased from CIN1 (80% weak intensity) to CIN2 (83.3% moderate), CIN3 (57.1% strong) and ICC (100% very strong). It was absent in normal cervical tissue and weak in 71.4% of condyloma. The mean scores of TLR9 expression were compared using the Kruskall-Wallis test and there was a statistical significance between normal tissue and condyloma as well as between condyloma, CINs and ICC. These results suggest that TLR9 may play a role in progression of cervical neoplasia in Tunisian patients and could represent a useful biomarker for malignant transformation of cervical squamous cells.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6109-6113
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• 2014

Background: Breast cancer is a heterogeneous disease with molecular subtypes that have biological distinctness and different behavior. They are classified into luminal A, luminal B, Her-2 and triple negative/basal-like molecular subtypes. Most of breast cancers reported in Indonesia are already large size, with high grade or late stage but the clinicopathological features of different molecular subtypes are still unclear. They need to be better clarified to determine proper treatment and prognosis. Aim: To elaborate the clinicopathological features of molecular subtypes of breast cancers in Indonesian women. Materials and Methods: A retrospective cross-sectional study of 84 paraffin-embedded tissues of breast cancer samples from Dr. Sardjito General Hospital in Central Java, Indonesia was performed. Expression of ER, PR, Her-2 and Ki-67 was analyzed to classify molecular subtypes of breast cancer by immunohistochemistry. The relation of clinicopathological features of breast cancers with molecular subtypes of luminal A, luminal B, Her-2 and triple negative/basal-like were analyzed using Pearson's Chi-Square test. A p-value of <0.05 was considered statistically significant. Results: Case frequency of luminal A, Luminal B, Her-2+ and triple negative/basal-like subtypes were 38.1%, 16.7%, 20.2% and 25%, respectively. Significant difference was found in breast cancer molecular subtypes in regard to age, histological grade, lymph node status and staging. However it showed insignificant result in regard to tumor size. Luminal A subtype of breast cancer was commonly found in >50 years old women (p:0.028), low grade cancer (p:0.09), negative lymph node metastasis (p:0.034) and stage III (p:0.017). Eventhough the difference was insignificant, luminal A subtype breast cancer was mostly found in small size breast cancer (p:0.129). Her-2+ subtype breast cancer was more commonly diagnosed with large size, positive lymph node metastasis and poor grade. Triple negative/basal-like cancer was mostly diagnosed among <50 years old women. Conclusions: This study suggests that immunohistochemistry-based subtyping is essential to classify breast carcinoma into subtypes that vary in clinicopathological features, implying different therapeutic options and prognosis for each subtype.

• Asian Pacific Journal of Cancer Prevention
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• 제15권8호
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• pp.3651-3657
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• 2014

Hepatocellular carcinoma (HCC) has a relatively higher incidence in many countries of Asia. Globally, HCC has a high fatality rate and short survival. Epirubicin, a doxorubicin analogue, may be administered alone or in combination with other agents to treat primary liver cancer and metastatic diseases. However, the toxic effects of epirubicin to normal tissues and cells have been one of the major obstacles to successful cancer chemotherapy. Here, we investigated the effects of epirubicin in combination with kappa-selenocarrageenan on mice with H22 implanted tumors and HepG-2 cell proliferation, immune organ index, morphology, cell cycle and related protein expressions in vivo and in vitro with sequential drug exposure. The inhibitory rate of tumor growth in vivo was calculated. Drug sensitivity was measured by MTT assay, and the King's principle was used to evaluate the interaction of drug combination. Morphological changes were observed by fluorescent microscopy. Cell cycle changes were analyzed by flow cytometry. Expression of cyclin A, Cdc25A and Cdk2 were detected by Western blotting. In vivo results demonstrated that the inhibitory rate of EPI combined with KSC was higher than that of KSC or EPI alone, and the Q value indicated an additive effect. In addition, KSC could significantly raise the thymus and spleen indices of mice with H22 implanted tumors. In the drug sensitivity assay in vitro, exposure to KSC and EPI simultaneously was more effective than exposure sequentially in HepG-2 cells, while exposure to KSC prior to EPI was more effective than exposure to EPI prior to KSC. Q values showed an additive effect in the simultaneous group and antagonistic effects in the sequential groups. Morphological analysis showed similar results to the drug sensitivity assay. Cell cycle analysis revealed that exposure to KSC or EPI alone arrested the cells in S phase in HepG-2 cells, exposure to KSC and EPI simultaneously caused accumulation in the S phase, an effect caused by either KSC or EPI. Expression of cyclin A, Cdc25A and Cdk2 protein was down-regulated following exposure to KSC and EPI alone or in combination, exposure to KSC and EPI simultaneously resulting in the lowest values. Taken together, our findings suggest that KSC in combination with EPI might have potential as a new therapeutic regimen against HCC.