• Animal Bioscience
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• 제35권7호
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• pp.989-998
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• 2022

Objective: This study investigated the effects of intrauterine growth restriction (IUGR) during late pregnancy on the cell growth, proliferation, and differentiation in ovine fetal thymuses. Methods: Eighteen time-mated Mongolian ewes with singleton fetuses were allocated to three groups at d 90 of pregnancy: restricted group 1 (RG1, 0.18 MJ ME/body weight [BW]^0.75/d, n = 6), restricted group 2 (RG2, 0.33 MJ ME/BW^0.75/d, n = 6) and control group (CG, ad libitum, 0.67 MJ ME/BW^0.75/d, n = 6). Fetuses were recovered at slaughter on d 140. Results: The G0/G1 phase cell number in fetal thymus of the RG1 group was increased but the proliferation index and the expression of proliferating cell nuclear antigen (PCNA) were reduced compared with the CG group (p<0.05). Fetuses in the RG1 group exhibited decreased growth hormone receptor (GHR), insulin-like growth factor 2 receptor (IGF-2R), and their mRNA expressions (p<0.05). For the RG2 fetuses, there were no differences in the proliferation index and PCNA expression (p>0.05), but growth hormone (GH) and the mRNA expression of GHR were lower than those of the CG group (p<0.05). The thymic mRNA expressions of cyclin-dependent protein kinases (CDKs including CDK1, CDK2, and CDK4), CCNE, E2-factors (E2F1, E2F2, and E2F5) were reduced in the RG1 and RG2 groups (p<0.05), and decreased mRNA expressions of E2F4, CCNA, CCNB, and CCND were occurred in the RG1 fetuses (p<0.05). The decreased E-cadherin (E-cad) as a marker for epithelial-mesenchymal transition (EMT) was found in the RG1 and RG2 groups (p<0.05), but the OB-cadherin which is a marker for activated fibroblasts was increased in fetal thymus of the RG1 group (p<0.05). Conclusion: These results indicate that weakened GH/IGF signaling system repressed the cell cycle progression in G0/G1 phase in IUGR fetal thymus, but the switch from reduced E-cad to increased OB-cadherin suggests that transdifferentiation process of EMT associated with fibrogenesis was strengthened. The impaired cell growth, retarded proliferation and modified differentiation were responsible for impaired maturation of IUGR fetal thymus.

• Asian Pacific Journal of Cancer Prevention
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• 제15권11호
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• pp.4539-4543
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• 2014

Since the epigenetic alteration in tumor cells can be reversed by the dietary polyphenol quercetin (Q) or butyrate (B) with chemopreventive activity, suggesting that Q or B can be used for chemopreventive as well as therapeutic agent against tumors. In this study the polyphenol flavonoid quercetin (Q) or sodium butyrate (B) suppressed human esophageal 9706 cancer cell growth in dose dependent manner, and Q combined with B (Q+B) could further inhibit Eca9706 cell proliferation than that induced by Q or B alone, compared with untreated control group (C) in MTT assay. The reverse expressions of global DNMT1, $NF-{\kappa}Bp65$, HDAC1 and Cyclin D1 were down-regulated, while expressions of caspase-3 and $p16INK4{\alpha}$ were up-regulated, compared with the C group in immunoblotting; the down-regulated HDAC1-IR (-immunoreactivity) with nuclear translocation, and up-regulated E-cadherin-IR demonstrated in immunocytochemistry treated by Q or B, and Q+B also displayed further negatively and positively modulated effects compared with C group. The order of methylation specific (MS) PCR of $p16INK4{\alpha}$: C>B/Q>Q+B group, while the order of E-cadherin expression level was contrary, Q+B>Q/B>C group. Thus, Q/B, especially Q+B display reverse effect targeting both altered DNA methylation and histone acetylation, acting as histone deacetylase inhibitor mediated via epigenetic-$NF-{\kappa}B$ cascade signaling.

• Asian Pacific Journal of Cancer Prevention
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• 제17권5호
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• pp.2655-2660
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• 2016

Background: Prostate cancer is the second most common male cancer and remains a leading cause of cancer death worldwide. Heterogeneity regarding recurrence, tumor progression and therapeutic response reflects the inadequacy of traditional prognostic factors and underlies interest in new genetic and molecular markers. In this work, we studied the prognostic value of the expression of 9 proteins, Ki-67, p53, Bcl-2, PSA, HER2, E-cadherin, $p21^{WAF1/Cip1}$, $p27^{Kip1}$ and $p16^{ink4a}$ in prostate cancer. Materials and Methods: We conducted a retrospective study of 50 prostate cancers diagnosed in Pathology Department of Farhet Hached Hospital, Sousse, Tunisia, during a period of 12 months. Clinico-pathological data and survival were investigated. Protein expression was analyzed by immunohistochemistry on archived material. Results: Expression or over-expression of Ki-67, p53, Bcl-2, PSA, HER2, E-Cadherin, $p21^{WAF1/Cip1}$, $p27^{Kip1}$ and $p16^{ink4a}$ was observed in 68%, 24%, 32%, 78%, 12%, 90%, 20%, 44% and 56% of cases, respectively. Overall five-year survival was 68%. A statistically significant correlation was observed between death occurrence and advanced age (p=0.018), degree of tumor differentiation (p=0.0001), perineural invasion (p=0.016) and metastasis occurrence (p=0.05). Death occurrence was significantly correlated with the expression of p53 (p=0.007), Bcl-2 (p=0.02), Ki-67 (p=0.05) and $p27^{Kip1}$ (p=0.04). Conclusions: The p53, Bcl-2, Ki-67 and $p27^{Kip1}$ proteins may be useful additional prognostic markers for prostate cancer. The use of these proteins in clinical practice can improve prognosis prediction, disease screening and treatment response of prostatic cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제17권5호
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• pp.2415-2421
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• 2016

E-cadherin (CDH1) genetic variations alter gene transcriptional activity of epithelial cells in vitro and may cause susceptibility to various cancers. Associations of CDH1 -160C>A polymorphism with various cancers have been widely reported. However, the results are controversial and inconsistent. To derive a more accurate estimation of the relationship, a meta-analysis was performed with regard to gastrointestinal (GI) cancer risk. Eligible studies were identified through a search of PubMed database until December 2015. Associations between the CDH1 -160C>A polymorphism and GI cancer risk was considered by odds ratios (ORs) together with their 95% confidence intervals (CIs). A total of 31 studies including 11,606 cases and 12,655 controls were involved in this meta-analysis. Overall, this meta-analysis showed no association between CDH1 -160C>A polymorphism and GI cancer risk (A vs. C: OR = 1.08, 95%CI = 0.98-1.18, P = 0.086;CA vs. CC: OR = 1.09, 95%CI = 0.97-1.22, P = 0.118; AA vs. CC: OR = 1.10, 95%CI = 0.89-1.35, P = 0.356; AA vs. CC + CA: OR = 1.06, 95%CI = 0.96-1.18, P = 0.207; CA+AA vs. CC: OR = 1.01, 95%CI = 0.84-1.22, P = 0.89). In subgroup analysis, similar results were found. In conclusion, this meta-analysis has demonstrated that there is a lack of association of the CDH1-160C>A polymorphism with GI cancer susceptibility.

• 생명과학회지
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• 제20권12호
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• pp.1784-1791
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• 2010

본 연구에서는 AGS 인체 위암세포에서 톳 에탄올 추출물(EHF)의 항침윤성과 tight junctions (TJs)의 tightening과의 관계를 조사하였다. EHF에 의한 AGS 위암세포의 증식억제와 연관된 세포이동성 및 침윤성의 감소는 transepithelial electrical resistance의 증가와 연계된 Js의 tightness 증가와 연관성이 있었다. EHF는 matrix metalloprotease (MMP)-2 및 -9의 활성을 억제하였으며, 이는 MMPs의 mRNA 및 단백질 발현 감소에 의한 것이었으나 tissue inhibitor of metalloproteinase (TIMP)-1 및 -2의 mRNA 발현은 증가시켰다. 또한 EHF는 TJs의 주요 조절인자인 claudin family 단백질들(claudin-1, -3 및 -4)의 발현을 감소시켰으며, insulin like growth factor-1 receptor 단백질은 감소된 반면 thrombospondin-1 및 E-cadherin의 발현은 증가되었다. 본 연구의 결과는 톳 추출물이 암의 전이를 효과적으로 억제하는 효능이 있음을 보여주는 결과이다.

• Reproductive and Developmental Biology
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• 제38권4호
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• pp.165-170
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• 2014

Cows may suffer impaired ovarian function, often accompanied by reduced conception rates and increased embryonic loss. Cystic ovarian disease (COD) is one of the most frequently diagnosed gynecological findings in dairy cattle. It causes temporary infertility and is likely to affect reproduction as well as production parameters in cattle. Therefore, the purpose of this study was to determine the expression patterns of apoptosis (Bcl-2, Bax), implantation (E-cadherin) and immune related proteins (TNF-${\alpha}$, IL-10) in uterine endometrium of Hanwoo (Korean native cattle) with ovarian cyst and normal ovarian follicles. In the Western blot analysis, the expression of anti-apoptotic Bcl-2 protein was significantly higher in endometrium with normal ovarian follicles, whereas expression of pro-apoptotic Bax protein was significantly lower. Also, the expressions of E-cadherin and TNF-${\alpha}$ proteins were significantly higher in uterine endometrium with normal ovarian follicles. On the other hand, the expression of IL-10 protein was significantly lower in uterine endometrium with normal ovarian follicles. Taken together, our results provided that the expressions of apoptosis, adhesion and immune related proteins in uterine endometrium with ovarian cyst were showed the aberrant patterns, and we suggest that different expression changes of these proteins may be affect to pregnancy ability of cattle.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9805-9812
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• 2014

Radixin, a member of the ERM (ezrin-radixin-moesin) family, plays important roles in cell motility, invasion and tumor progression. It is expressed in a variety of normal and neoplastic cells, including many types of epithelial and lymphoid examples. However, its function in glioblastomas remains elusive. Thus, in this study, radixin gene expression was first examined in the glioblastoma cells, then suppressed with a lentivirus-mediated short-hairpin RNA (shRNA) method.We found that there were high levels of radixin expression in glioblastoma U251cells. Radixin shRNA caused down-regulation of radixin gene expression and when radixin-silenced cells were implanted into nude mice, tumor growth was significantly inhibited as compared to blank control cells or nonsense shRNA cells. In addition, microvessel density in the tumors was significantly reduced. Thrombospondin-1 (TSP-1) and E-cadherin were up-regulated in radixin- suppressed glioblastoma U251 cells. In contrast, MMP9 was down-regulated. Taken together, our findings suggest that radixin is involved in GBM cell migration and invasion, and implicate TSP-1, E-cadherin and MMP9 as metastasis-inducing factors.

• Asian Pacific Journal of Cancer Prevention
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• 제16권7호
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• pp.2777-2783
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• 2015

Background: Nestin is associated with neoplastic transformation. However, the mechanisms by which nestin contributes regarding invasion and malignancy of gastric adenocarcinoma (GAC) remain unknown. Recent studies have shown that the epithelial-mesenchymal transition (EMT) is important in invasion and migration of cancer cells. In the present study, we aimed to investigate the expression of nestin and its correlation with EMT-related proteins in GAC. Materials and Methods: The expression of nestin and EMT-related proteins was examined in GAC specimens and cell lines by immunohistochemistry and Western blotting. Clinicopathological features and survival outcomes were retrospectively analyzed. Results: Positive nestin immunostaining was most obviously detected in the cytoplasm, nucleus or both cytoplasm and nucleus of tumor cells in 19.2% (24/125) of GAC tissues, which was significantly higher than that in normal gastric mucosa tissues (1.7%, 1/60) (p=0.001). Nestin expression was closely related to several clinicopathological factors and EMT-related proteins (E-cadherin, vimentin and Snail) and displayed a poor prognosis. Interestingly, simultaneous cytoplasmic and nuclear nestin expression correlated with EMT-related proteins (E-cadherin, vimentin and Snail) (p<0.05) and lymph node metastasis (p=0.041) and a shorter survival time (p<0.05), but this was not the case with cytoplasmic or nuclear nestin expression. Conclusions: Nestin, particularly expression in both cytoplasm and nucleus, might be involved in regulating EMT and malignant progression in GAC, with potential as an unfavorable indicator in tumor diagnosis and a target for clinical therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7425-7432
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• 2014

Aim: To investigate the expression of protein kinase $CK2{\alpha}$ ($CK2{\alpha}$) in human thyroid disease and its relationship with thyroid cancer metastasis. Materials and Methods: Using immunohistochemistry we measured the expression of $CK2{\alpha}$ in 76 benign and malignant human thyroid cancer tissues, including 10 pairs of papillary carcinoma tissues with or without lymph node cancerous metastasis and similarly 10 pairs of lymph nodes. Results: The expression of $CK2{\alpha}$ was found to be higher in thyroid carcinoma cases (papillary carcinoma, follicular carcinoma, anaplastic carcinoma and medullary carcinoma) than in ones such as chronic lymphocytic thyroiditis, nodular goiter and adenoma. These findings were also confirmed by RT-PCR and Western blotting. More strikingly, elevated expression of $CK2{\alpha}$ in thyroid papillary carcinoma tissues was not only significantly associated with lymph node cancerous metastasis and clinical stage of thyroid cancers; but also correlated with epithelial-mesenchymal transition (EMT) and high tenascin C (TNC) expression. In addition, EMT and high TNC expression in thyroid carcinoma tissues was significantly associated with lymph node cancerous metastasis. Conclusions: Elevated expression of nuclear $CK2{\alpha}$ is a poor prognosis indicator in lymph node cancerous metastasis of human thyroid cancers.

• Asian Pacific Journal of Cancer Prevention
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• 제15권20호
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• pp.8679-8684
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• 2014

CD133 was recently reported to be a cancer stem cell and prognostic marker. Quercetin is considered as a potential chemopreventive agent due to its involvement in suppression of oxidative stress, proliferation and metastasis. In this study, the expression of CD133/CD44 in esophageal carcinomas and Eca109/9706 cells was explored. In immunoflurorescence the locations of $CD133^+$ and multidrug resistance 1 $(MDR1)^+$ in the same E-cancer cells were coincident, mainly in cytomembranes. In esophageal squamous cell carcinomas detected by double/single immunocytochemistry, small $CD133^+$ cells were located in the basal layer of stratified squamous epithelium, determined as CSLC (cancer stem like cells); $CD44^+$ surrounding the cells appeared in diffuse pattern, and the larger $CD44^+$ (hi) cells were mainly located in the prickle cell layer of the epithelium, as progenitor cells. In E-cancer cells exposed to nanoliposomal quercetin (nLQ with cytomembrane permeability), down-regulation of NF-${\kappa}Bp65$, histone deacetylase 1 (HDAC1) and cyclin D1 and up-regulation of caspase-3 were shown by immunoblotting, and attenuated HDAC1 with nuclear translocation and promoted E-cadherin expression were demonstrated by immunocytochemistry. In particular, enhanced E-cadherin expression reflected the reversed epithelial mesenchymal transition (EMT) capacity of nLQ, acting as cancer attenuator/preventive agent. nLQ acting as an HDAC inhibitor induced apoptotic cells detected by TUNEL assay mediated via HDAC-NF-${\kappa}B$ signaling. Apoptotic effects of liposomal quercetin (LQ, with cytomembrane-philia) combined with CD133 antiserum were also detected by CD133 immunocytochemistry combined with TUNEL assay. The combination could induce greater apoptotic effects than nLQ induced alone, suggesting a novel anti-CSC treatment strategy.