• Asian Pacific Journal of Cancer Prevention
• /
• 제15권15호
• /
• pp.6397-6403
• /
• 2014

Background: Aberrant promoter hypermethylation has been recognized in human breast carcinogenesis as a frequent molecular alteration associated with the loss of expression of a number of key regulatory genes and may serve as a biomarker. The E-cadherin gene (CDH1), mapping at chromosome 16q22, is an intercellular adhesion molecule in epithelial cells, which plays an important role in establishing and maintaining intercellular connections. The aim of our study was to assess the methylation pattern of CDH1 and to correlate it with the expression of E-cadherin, clinicopathological parameters and hormone receptor status in breast cancer patients of Kashmir. Materials and Methods: Methylation specific PCR (MSP) was used to determine the methylation status of CDH1 in 128 invasive ductal carcinomas (IDCs) paired with the corresponding normal tissue samples. Immunohistochemistry was used to study the expression of E-cadherin, ER and PR. Results: CDH1 hypermethylation was detected in 57.8% of cases and 14.8% of normal adjacent controls. Reduced levels of E-cadherin protein were observed in 71.9% of our samples. Loss of E-cadherin expression was significantly associated with the CDH1 promoter region methylation (p<0.05, OR=3.48, CI: 1.55-7.79). Hypermethylation of CDH1 was significantly associated with age at diagnosis (p=0.030), tumor size (p=0.008), tumor grade (p=0.024) and rate of node positivity or metastasis (p=0.043). Conclusions: Our preliminary findings suggest that abnormal CDH1 methylation occurs in high frequencies in infiltrating breast cancers associated with a decrease in E-cadherin expression. We found significant differences in tumor-related CDH1 gene methylation patterns relevant to tumor grade, tumor size, nodal involvement and age at diagnosis of breast tumors, which could be extended in future to provide diagnostic and prognostic information.

• 한국식품조리과학회지
• /
• 제15권2호
• /
• pp.108-113
• /
• 1999

참마(Dioscorea japonica Thunb.), 달개비(Commelina communis L.) 전초, 하늘타리(Trichosanthes kiri1owii Max.) 및 둥굴레(Polygonatum odoratum var. Plurifloum Ohwi) 뿌리의 MeOH 추출물과 petroleum ether/diethyl ether 및 EtOAc 가용성 용매분획물을 인체 폐암 및 난소선암세포주에 적용하여 암세포주 성장율을 측정하였다. 실험 결과 하늘타리 뿌리의 MeOH 추출물이 인체 폐암 및 난소선암세포주에 대해 모두 강한 성장억제를 보여주었으며 40$\mu\textrm{g}$/ml의 농도에서 30% 이하의 성장율을 나타내었다. 다음으로 용매분획물에 대한 세포독성은 하늘타리의 EtOAc 가용성 분획물에서 폐암과 난소선암세포주에 대한 성장억제율이 30% 이하로 매우 높게 나타나고 있으며, 참마의 EtOAc 가용성 용매분획물이 인체 폐암세포주에 대하여 30% 이하의 높은 성장억제를 나타내고 있다. 그밖에 달개비 전초의 EtOAc 가용성 분획물이 인체 폐암세포주에 대해 30%에서 60%의 성장율을 나타내고, 둥굴레 뿌리의 petroleum ether/diethyl ether 및 EtOAc 분획물이 인체 난소선암세포주에 대해 동일한 정도의 성장율을 보여주고 있다. 이상의 결과를 통해 한국산 야생식용식물로 부터 세포 독성작용을 갖는 새로운 식품 개발의 가능성을 확인할 수 있었을 뿐 아니라, 이를 위한 지속적인 연구로서 폐암 및 난소선암세포주에 대한 세포독성 작용이 가장 강하게 나타난 하늘타리 및 참마의 EtOAc 용매 세분획물을 이용하여 활성이 높은 순수 물질을 분리하므로 추후 새로운 항암활성 물질 연구를 위한 후보식물로서의 개발가능성을 보여주었다.

• Journal of Ginseng Research
• /
• 제38권1호
• /
• pp.8-15
• /
• 2014

Helicobacter pylori-induced gastric inflammation includes induction of inflammatory mediators interleukin (IL)-8 and inducible nitric oxide synthase (iNOS), which are mediated by oxidant-sensitive transcription factor NF-${\kappa}B$. High levels of lipid peroxide (LPO) and increased activity of myeloperoxidase (MPO), a biomarker of neutrophil infiltration, are observed in H. pylori-infected gastric mucosa. Panax ginseng Meyer, a Korean herb medicine, is widely used in Asian countries for its biological activities including anti-inflammatory efficacy. The present study aims to investigate whether Korean Red Ginseng extract (RGE) inhibits H. pylori-induced gastric inflammation in Mongolian gerbils. One wk after intragastric inoculation with H. pylori, Mongolian gerbils were fed with either the control diet or the diet containing RGE (200 mg RGE/gerbil) for 6 wk. The following were determined in gastric mucosa: the number of viable H. pylori in stomach; MPO activity; LPO level; mRNA and protein levels of keratinocyte chemoattractant factor (KC, a rodent IL-8 homolog), IL-$1{\beta}$, and iNOS; protein level of phospho-$I{\kappa}B{\alpha}$(which reflects the activation of NF-${\kappa}B$); and histology. As a result, RGE suppressed H. pylori-induced mRNA and protein levels of KC, IL-$1{\beta}$, and iNOS in gastric mucosa. RGE also inhibited H. pylori-induced phosphorylation of $I{\kappa}B{\alpha}$ and increases in LPO level and MPO activity of gastric mucosa. RGE did not affect viable H. pylori colonization in the stomach, but improved the histological grade of infiltration of poly-morphonuclear neutrophils, intestinal metaplasia, and hyperplasia. In conclusion, RGE inhibits H. pyloriinduced gastric inflammation by suppressing induction of inflammatory mediators (KC, IL-$1{\beta}$, iNOS), MPO activity, and LPO level in H. pylori-infected gastric mucosa.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권10호
• /
• pp.5033-5036
• /
• 2012

Objective: To study the relationship between expression of $p57^{KIP2}$ and prognosis and other clinicopathological parameters in invasive breast cancers. Methods: We assessed the expression of $p57^{KIP2}$ in 89 cases of invasive breast cancer and 20 cases of normal breast tissue by immunohistochemical methods and analyzed the results with SPSS software (ver. 16.0). Result: The positive expression rates of $p57^{KIP2}$ protein in the invasive breast cancers and surrounding normal tissue were 30.3% (27/89) and 65% (13/20), respectively. Cases with no $p57^{KIP2}$ expression exhibited a significantly higher post-operative distant metastasis rate than those with $p57^{KIP2}$ expression (37.9% vs. 14.8%; P = 0.01). DFS analysis showed that $p57^{KIP2}$-/C-erbB-2+ tumors also exhibited a significantly higher post-operative distant metastasis rate than the other groups (66.7% vs. 29.2%; P = 0.007), as did $p57^{KIP2}$-/p53+ tumors (64.3% vs. 22.7%; P = 0.001). Survival analysis revealed that $p57^{KIP2}$ was associated with breast cancer-specific survival overall (P = 0.045, log-rank test). Subgroup analysis demonstrated that individuals with $p57^{KIP2}$-/C-erbB-2+tumors experienced significantly worse post-operative survival than those with $p57^{KIP2}$-/C-erbB-2- or other tumors (P = 0.006, log-rank test). $p57^{KIP2}$-/p53+ tumors were associated with significantly worse post-operative survival than $p57^{KIP2}$-/p53- or other tumors (P = 0.001, log-rank test). Cox regression analysis showed that $p57^{KIP2}$ was a non-independent prognostic factor for breast cancer (P = 0.303). Conclusions: $p57^{KIP2}$ is expressed at low levels in invasive breast cancer and is associated with better overall survival rate and disease-free survival in breast cancer patients, but it was a non-independent prognostic factor for breast cancer. Thus, the connection between $p57^{KIP2}$/p53 and $p57^{KIP2}$/C-erbB-2 may provide biomarkers for breast cancer.

• Tuberculosis and Respiratory Diseases
• /
• 제54권5호
• /
• pp.485-494
• /
• 2003

배경 : Glutathione S-transferase(GST)는 발암 전구물질의 해독에 관여하는 효소로, GSTM1과 GSTT1 소실형을 갖는 개체는 폐암의 감수성이 높은 것으로 생각된다. 여성 폐암은 위험 인자, 조직형 등의 역학적 특성이 남성과 차이가 많기 때문에 유전적 감수성 인자 또한 차이가 있을 것으로 생각된다. 이에 저자들은 한국인에서 GSTM1과 GSTT1 유전자형과 폐암 발생 위험도의 상관 관계를 남성과 여성을 분리하여 조사하였다. 방법 : 1997년 1월부터 1999년 12월까지 경북대학교 병원에서 폐암으로 확진된 253명의 환자를 대상으로 하였으며, 대조군은 경북대학교 병원 건강 검진센터를 방문한 검진자들을 대상으로 하였다. GSTM1과 GSTT1의 유전자형은 말초 혈액에서 DNA를 추출한 후 다중중합효소 연쇄 반응(multiplex PCR)을 통하여 조사하였다. 결과 : 남성에서는 GSTM1과 GSTT1 유전자형에 따른 폐암 발생 위험도의 유의한 차이가 없었다. 여성에서는 GSTM1 유전자형과 폐암 발생 위험도는 유의한 차이가 없었으나, GSTT1 소실형의 빈도는 폐암군 70.3%, 대조군 55.3%로 폐암군에서 유의하게 높았다 [odds ratio(OR, 대응비)=2.18, 95% confidence interval(CI, 신뢰구간)=1.21-3.93). 흡연력과 연령에 따라 층화분석한 경우 GSTT1 소실형은 60세 이하(OR=4.82, 95% CI=1.61-14.4)와 비흡연자(OR=4.29, 95% CI=1.94-9.48]에서 여성 폐암 위험도와 유의한 관계가 있었다. 결론 : GSTT1 유전자형은 한국인 비흡연 여성에서 폐암의 위험도를 결정하는 유전적 인자로 생각된다.

• BMB Reports
• /
• 제34권2호
• /
• pp.123-129
• /
• 2001

Cellular response to ionizing radiation is affected by cell types, radiation doses, and post-irradiation time. Based on the trypan blue dye exclusion assay in normal oral mucosal cells (OM cells), a 48 h post-irradiation was sufffcient and an adequate time point for the evaluation of radiation sensitivity Its $LD_{50}$ was approximately 1.83 Gy To investigate possible biomarkers useful for the biological radiodosimetry of normal epithelial cells (p53, c-fos, cyclin D1, cdc-2, pRb) EGF receptor phosphorylation and Erk activation were evaluated at different radiation doses and different post-irradiation times. From 0.5 Gy, p53 was accumulated in the nucleus of basal cells of the OM raft culture at 4 h post-irradiation and sustained up to 24 h post-irradiation, which suggests that radiation-induced apoptosis or damage repair was not yet completed. The number of p53 positive cells and biosynthesis of p53 were correlated with radiation doses. Both cyclin D1 and c-fos were only transiently induced within 1 h post-irradiation. Cyclin D1 was induced at all radiation doses. However, cfos induction was highest at 0.1 Gy, approximately 7.3 fold more induction than the control, whose induction was reduced in a reverse correlation with radiation dose. The phosphorylation pattern of cdc-2 and pRb were unaffected by radiation. In contrast to A431 tails overexpressing the EGF receptor approximately 8.5 fold higher than normal epithelial, the OM cells reduced the basal level of the EGF receptor phosphorylation in a radiation dose dependent fashion. In conclusion, among radiation-induced biomolecules, the p53 nuclear accumulation may be considered for the future development of a useful marker far biological radiodosimetry in normal epithelial tissue since it was sustained for a longer period and showed a dose response relationship. Specific c-fos induction at a low dose may also be an important finding in this study It needs to be studied further for the elucidation of its possible connection with the low dose radio-adaptive response.

• 대한두경부종양학회지
• /
• 제27권2호
• /
• pp.190-197
• /
• 2011

Background and Objective : Radiation resistance(RR) is one of main determinants of treatment outcome in oral squamous cell carcinoma(OSCC), but accurate prediction of RR is difficult. We aim to establish RR OSCC cell lines and identify genes related with RR by a measurement of altered gene expression after inducing RR. Material and Methods : OSCC cell lines, SCC15, SCC25 and QLL1, were treated with 2Gy radiation per session, and parts of them were alive in finally accumulated dosage of 60Gy through 30 times repetition of radiotherapy for inducing RR cell lines. We compared results of cDNA array and proteomics in non-radiated cell lines and RR cell lines to detect changes of gene expression. Western blot was used for the validation of results. Results : cDNA array revealed 265 commonly up-regulated genes and 268 commonly down-regulated genes in 3 RR cell lines comparing their non-radiated counterpart. Among them, 30 cancer related genes were obtained. Proteomics showed 51 commonly altered protein expressions in 3 RR cell lines and 18 cancer related proteins were obtained. Among the detected genes, we found NM23-H1 and PA2G4 were over-expressed in both cDNA array and proteomics. Western blot showed increased expression of NME1 in RR cell lines but not in PA2G4. Conclusion: We concluded that NM23-H1 may be a candidate of RR related gene and over-expression of NM23-H1 could be a biomarker to predict RR in OSCC.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권23호
• /
• pp.10217-10223
• /
• 2015

Hyperactivated ${\alpha}2$-6-sialylation on N-glycans due to overexpression of the Golgi enzyme ${\beta}$-galactoside: ${\alpha}2$-6-sialyltransferase (ST6Gal-I) often correlates with cancer progression, metastasis, and poor prognosis. This study was aimed to determine the association between ST6Gal-I expression and the risk of recurrence and survival of patients with localized clear-cell renal cell carcinoma (ccRCC) following surgery. We retrospectively enrolled 391 patients (265 in training cohort and 126 in validation cohort) with localized ccRCC underwent nephrectomy at a single center. Tissue microarrays were constructed for immunostaining of ST6Gal-I. Prognostic value and clinical outcomes were evaluated. High ST6Gal-I expression was associated with Fuhrman grade (p<0.001 and p=0.016, respectively) and the University of California Los-Angeles Integrated Staging System (UISS) score (p=0.004 and p=0.017, respectively) in both cohorts. Patients with high ST6Gal-I expression had significantly worse overall survival (OS) (p<0.001 and p<0.001, respectively) and recurrence free survival (RFS) (p<0.001 and p=0.002, respectively) than those with low expression in both cohorts. On multivariate analysis, ST6Gal-I expression remained associated with OS and RFS even after adjusting for the UISS score. Stratified analysis suggested that the association is more pronounced among patients with low and intermediate-risk disease defined by the UISS score. High ST6Gal-I expression is a potential independent adverse predictor of survival and recurrence in ccRCC patients, and the prognostic value is most prominent in those with low and intermediate-risk disease defined by the UISS score.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권12호
• /
• pp.4969-4976
• /
• 2014

Background: miR-152 is involved in the genesis and development of several malignancies. However, its role in HCC has not been fully clarified. The aim of this study was to investigate the clinicopathological significance of miR-152 and its effect on the malignant phenotype of HCC cells. Methods: miR-152 expression was detected using real-time quantitative RT-PCR in 89 pairs of HCC formalin-fixed paraffin-embedded and their adjacent tissues. Functionally, in vitro effects and mechanisms of action of miR-152 on proliferation, viability, caspase activity, apoptosis and motility were explored in HepG2, HepB3 and SNU449 cells, as assessed by spectrophotometry, fluorimetry, fluorescence microscopy, wound-healing and Western blotting, respectively. Results: miR-152 expression in HCC was downregulated remarkably compared to that in adjacent hepatic tissues. miR-152 levels in groups of advanced clinical stage, larger tumor size and positive HBV infection, were significantly lower than in other groups. A miR-152 mimic could suppress cell growth, inhibit cell motility and increase caspase activity and apoptosis in HCC cell lines. Furthermore, Western blotting showed that the miR-152 mimic downregulated Wnt-1, DNMT1, ERK1/2, AKT and TNFRS6B signaling. Intriguingly, inverse correlation of TNFRF6B and miR-152 expression was found in HCC and bioinformatics confirmed that TNFRF6B might be a target of miR-152. Conclusions: Underexpression of miR-152 plays a vital role in hepatocarcinogenesis and lack of miR-152 is related to the progression of HCC through deregulation of cell proliferation, motility and apoptosis. miR-152 may act as a tumor suppressor miRNA by also targeting TNFRSF6B and is therefore a potential candidate biomarker for HCC diagnosis, prognosis and molecular therapy.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권8호
• /
• pp.3613-3618
• /
• 2014

Stathmin, also called oncoprotein 18, is a founding member of the family of microtubule-destabilizing proteins that play a critical role in the regulation of mitosis. At the same time stathmin has been recognized as one of responsible factors in cancer cells. The aim of this study was to assess stathmin status, its correlations with clinicopathological parameters and its role as a progosnostic marker in EC patients. The protein and mRNA levels of stathmin were examined byimmunohistochemistry (IHC) and in situ hybridization in 100EC tissues and adjacent noncancerous tissues. mRNA and protein expression of stathmin in three EC cell lines(EC9706, ECa109, EC1 commonly used in research) were also analyzed using immunocytochemistry, western blot and in situ hybridization. The prognostic value of Stathmin expression within the tumor tissues were assessed by Cox regression and Kaplan-Meier analysis. We showed that stathmin expression was significantly higher in EC tissues than in adjacent noncancerous tissues. High stathmin immunostaining score in the EC was positively correlated with tumor differentiation, Tumor invasion, Lymph node metastases, and TNM stage. In addition, we demonstrated that three EC cell lines examined, were constitutively expressing a high level of stathmin. Of those, EC-1 showed the strongest mRNA and protein expression for the stathmin analyzed. Kaplan-Meier analysis showed that significantly longer 5-year survival rate was seen in EC patients with high Stathmin expression, compared to those with low expression of Stathmin expression. Furthermore, multivariate Cox proportional hazard analyses revealed that Stathmin was an independent factors affecting the overall survival probability. In conclusion, our data provide a basis for the concept that stathmin might be associated with EC development and progression. High levels of Stathmin expression in the tumor tissues may be a good prognostic marker for patients with EC.