• Asian Pacific Journal of Cancer Prevention
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• 제15권7호
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• pp.3311-3317
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• 2014

Background: The consequence of Rho GDP dissociation inhibitor alpha (RhoGDI${\alpha}$) activity on migration and invasion of estrogen receptor positive ($ER^+$) and negative ($ER^-$) breast cancer cells has not been studied using the proteomic approach. Changes in expression of RhoGDI${\alpha}$ and other proteins interacting directly or indirectly with RhoGDI${\alpha}$ in MCF7 and MDA-MB-231, with different metastatic potentials is of particular interest. Materials and Methods: $ER^+$ MCF7 and ER- MDA-MB-231 cell lines were subjected to two-dimensional electrophoresis (2-DE) and spots of interest were identified by matrix-assisted laser desorption/ionization time of- flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry (MS) analysis after downregulation of RhoGDI${\alpha}$ using short interfering RNA (siRNA) and upregulated using GFP-tagged ORF clone of RhoGDI${\alpha}$. Results: The results showed a total of 35 proteins that were either up- or down-regulated in these cells. Here we identifed 9 and 15 proteins differentially expressed with silencing of RhoGDI${\alpha}$ in MCF-7 and the MDA-MB-231 cells, respectively. In addition, 10 proteins were differentially expressed in the upregulation of RhoGDI${\alpha}$ in MCF7, while only one protein was identified in the upregulation of RhoGDI${\alpha}$ in MDA-MB-231. Based on the biological functions of these proteins, the results revealed that proteins involved in cell migration are more strongly altered with RhoGDI-${\alpha}$ activity. Although several of these proteins have been previously indicated in tumorigenesis and invasiveness of breast cancer cells, some ohave not been previously reported to be involved in breast cancer migration. Hence, these proteins may serve as useful candidate biomarkers for tumorigenesis and invasiveness of breast cancer cells. Conclusions: Future studies are needed to determine the mechanisms by which these proteins regulate cell migration. The combination of RhoGDI${\alpha}$ with other potential biomarkers may be a more promising approach in the inhibition of breast cancer cell migration.

• Asian Pacific Journal of Cancer Prevention
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• 제15권13호
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• pp.5117-5121
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• 2014

Endocrine-disrupting chemicals (EDCs) have been reported to interfere with estrogen signaling. Exposure to these chemicals decreases the immune response and causes a wide range of diseases in animals and humans. Recently, many studies showed that licorice (Glycyrrhiza glabra) root extract (LRE) commonly called "gamcho" in Korea exhibits antioxidative, chemoprotective, and detoxifying properties. This study aimed to investigate the mechanism of action of LRE and to determine if and how LRE can alleviate the toxicity of EDCs. LRE was prepared by vacuum evaporation and freeze-drying after homogenization of licorice root powder that was soaked in 80% ethanol for 72 h. We used 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as an EDC, which is known to induce tumors or cancers; MCF-7 breast cancer cells were used as a tumorigenic model. These were treated with TCDD and various concentrations of LRE (0, 50, 100, 200, $400{\mu}g/mL$) for 24, 48, and 72 h. As a result, TCDD stimulated MCF-7 cell proliferation, but LRE significantly inhibited TCDD-induced MCF-7 cell proliferation in a dose- and time-dependent manner. Expression of TCDD toxicity-related genes, i.e., aryl hydrocarbon receptor (AhR), AhR nuclear translocator, and cytochrome P450 1A1, were subsequently down-regulated by LRE in a dose-dependent manner. Analysis of cell cycle distribution after treatment of MCF-7 cells with TCDD and various concentrations of LRE showed that LRE inhibited the proliferation of MCF-7 cells via G2/M phase arrest. Reverse transcription-polymerase chain reaction and Western blot analyses also revealed that LRE dose-dependently increased the expression of the tumor suppressor genes p53 and p27 and down-regulated the expression of cell cycle-related genes. These data suggest that LRE can mitigate the tumorigenic effects of TCDD in breast cancer cells by suppression of AhR expression and cell cycle arrest. Thus, LRE can be used as a potential toxicity-alleviating agent against EDC-mediated disease.

• Asian-Australasian Journal of Animal Sciences
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• 제17권5호
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• pp.598-602
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• 2004

The Tongcheng pig breed is a famous Chinese indigenous breed. The Ministry of Agriculture of China has filed it as 1 of 19 national key conservation breeds selected from more than 100 Chinese indigenous pig breeds in 2000. In order to improve the reproductive performance, it has been intensively selected to increase the litter size for about 10 years. The population randomly sampled from conservation nucleus of eight families in the Tongcheng pigs was genotyped for identification of their estrogen receptor locus polymorphisms with the PCR-RFLPs method. Only AB heterozygotes and BB homozygotes were detected, and $X^2$ test demonstrated that the locus was in disequilibrium at a significant level (p<0.05). In the present paper, the litter sizes in different parities were regarded as different traits. Holistic status of other unspecific and unidentified genes was estimated by using the statistical methods. Coefficients of kurtosis and skewness showed that the litter size still presented segregating characteristic in the 2nd, 5th, 7th, 8th and 9th parities. Analysis of homogeneity of variance between families confirmed the results for the 5th, 7th and 8th parities. The heritability of litter size for the 1st to 10th parities was estimated with paternal half-sib model and individual estimated breeding values (EBVs) were evaluated by a single trait animal model as well. We found that the averages of EBVs for litter size in each parity did not differ significantly between genotypes, despite the significant difference for original phenotype records in the 3rd, 4th and 5th parities (p<0.05 or p<0.01). The results may be explained by the deduction that the polymorphisms of ESR locus are no longer the important genetic base of litter size variation when the frequency of allele B accumulated in the experience of selection procedure, and further conferring that there exist special genes associated with litter size in the recent Tongcheng pigs population can be made.

• Asian-Australasian Journal of Animal Sciences
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• 제29권1호
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• pp.36-42
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• 2016

Milk-related traits (milk yield, fat and protein) have been crucial to selection of Holstein. It is essential to find the current selection trends of Holstein. Despite this, uncovering the current trends of selection have been ignored in previous studies. We suggest a new formula to detect the current selection trends based on single nucleotide polymorphisms (SNP). This suggestion is based on the best linear unbiased prediction (BLUP) and the Fisher's fundamental theorem of natural selection both of which are trait-dependent. Fisher's theorem links the additive genetic variance to the selection coefficient. For Holstein milk production traits, we estimated the additive genetic variance using SNP effect from BLUP and selection coefficients based on genetic variance to search highly selective SNPs. Through these processes, we identified significantly selective SNPs. The number of genes containing highly selective SNPs with p-value <0.01 (nearly top 1% SNPs) in all traits and p-value <0.001 (nearly top 0.1%) in any traits was 14. They are phosphodiesterase 4B (PDE4B), serine/threonine kinase 40 (STK40), collagen, type XI, alpha 1 (COL11A1), ephrin-A1 (EFNA1), netrin 4 (NTN4), neuron specific gene family member 1 (NSG1), estrogen receptor 1 (ESR1), neurexin 3 (NRXN3), spectrin, beta, non-erythrocytic 1 (SPTBN1), ADP-ribosylation factor interacting protein 1 (ARFIP1), mutL homolog 1 (MLH1), transmembrane channel-like 7 (TMC7), carboxypeptidase X, member 2 (CPXM2) and ADAM metallopeptidase domain 12 (ADAM12). These genes may be important for future artificial selection trends. Also, we found that the SNP effect predicted from BLUP was the key factor to determine the expected current selection coefficient of SNP. Under Hardy-Weinberg equilibrium of SNP markers in current generation, the selection coefficient is equivalent to $2^*SNP$ effect.

• Asian Pacific Journal of Cancer Prevention
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• 제17권7호
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• pp.3595-3600
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• 2016

Background: To investigate the association between preoperative pathological Ki-67 labeling index and serum tumor marker cancer antigen 15-3 (CA 15-3) with clinic-pathological parameters and treatment outcomes in early breast cancer. Materials and Methods: A retrospective study at 4 cancer centers in Saudi Arabia and Egypt was performed. Data were collected for female patients diagnosed with unilateral early breast cancer between March 2010 and October 2013. Cases treated with neoadjuvant chemotherapy (NACT) followed by surgery and radiotherapy were included. NACT included 6-8 cycles of anthracycline and taxane based regimens. Trastuzumab and hormonal treatments were added according to HER2 and hormone receptor status. Baseline serum CA15.3 and pathological Ki67 levels were evaluated and correlated with disease free survival (DFS) and overall survival (OS). Results: A total of 280 pts was included. The median age was 49 years (38-66 y) and median overall survival was 35 (20-38) months (mo). Estrogen receptors (ER), progesterone receptors (PR) and HER 2 receptors were positive in 233 (83.2%), 198 (70%) and 65 cases (23.2%), respectively. High preoperative Ki67 and CA15.3 were noted in 177 (63.2%) and 131 (46.8%). A total of 45 (16%) patients had distal or local recurrence and 24 (8.6%) died of their disease. Most of the relapsed cases had high preoperative Ki-67 (n=41, 91%) and CA15.3 (n=28, 62%) values. All of the patients who died had a high Ki-67 but CA15.3 was high in 9 (37%) only. Mean DFS/OS in patients with high preoperative Ki-67 was 32 months /32 months as compared to 37 months/35 months in those with normal Ki-67 (p<0.001). Correlation of preoperative CA15.3 and survival was statistically not significant. Conclusions:Preoperative Ki-67 can be a predictive and prognostic marker. Higher levels are associated with poor DFS and OS in patients with early BC.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5095-5099
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• 2013

Background: The overall incidence of breast cancer in South Asian countries, including Nepal, is low compared to Western countries. However, the incidence of breast cancer among young women is relatively high. Breast cancer in such cases is characterized by a relatively unfavorable prognosis and unusual pathological features. The aim of this study was to investigate clinico-pathological and biological characteristics in younger breast cancer patients (<40 years) and compare these with their older counterparts. Materials and Methods: Nine hundred and forty four consecutive female breast cancer patients, admitted to the Department of Surgery, Tribhuvan University Teaching Hospital, Kathmandu, Nepal between November 1997 and October 2012, were retrospectively analyzed. Results: Out of the 944 female breast cancer patients, 263 (27.9%) were <40 years. The mean age was $34.6{\pm}5.0$ years among younger patients compared to $54.1{\pm}9.9$ for those ${\geq}40$ years. The mean age at menarche was also significantly lower ($13.5{\pm}1.5$ vs $14.2{\pm}1.5$ years p=0.001) while the mean duration of symptoms was significantly longer (7.6 vs 6.5 months p=0.004). Family history of breast cancer was evident in 3.0% of the young women versus 0.3% in the older one. Mammography was performed less frequently in younger patients (59.7%), compared to older (74.4%), and was of diagnostic benefit in only 20% of younger patients compared to 85% of older ones. At diagnosis, the mean tumor diameter was significantly larger in young women ($5.0{\pm}2.5$ vs $4.5{\pm}2.4cm$, p=0.005). Axillary lymph nodes were positive in 73% of younger patients and 59% of older patients. In the younger group, the proportion of stage III or IV disease was higher (55.1% vs 47.1%, $p{\leq}0.05$). The proportion of breast conserving surgery was higher in young patients (25.1% vs 8.7%) and a higher proportion of younger patients receive neoadjuvant chemotherapy (9.9% vs 2.8%). The most common histological type was ductal carcinoma (93.1% vs 86%). The proportion of histological grade II or III was higher in younger patients (55.9% vs 24.5%). Similarly, in the younger group, lymphatic and vascular invasion was more common (63.2% vs 34.3% and 39.8% vs 25.4%, respectively). Patients in the younger age group exhibited lower estrogen and/or progesterone receptor positivity (34.7% vs 49.8%). Although statistically not significant, the proportion of triple negative tumors in younger age group was higher (22.4% vs 13.6%). Conclusions: Breast cancer in young Nepalese women represents over one quarter of all female breast cancers, many being diagnosed at an advanced stage. Tumors in young women exhibit more aggressive biological features. Hence, breast cancer in young women is worth special attention for earlier detection.

• Radiation Oncology Journal
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• 제26권1호
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• pp.10-16
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• 2008

목적: 조기 유방암에서 유방보존치료와 유방절제술의 치료 성적을 비교하고, 예후 인자를 알아보고자 하였다. 대상 및 방법: 1994년 9월부터 2002년 12월까지 본원에서 근치적 수술을 받은 병리학적 병기 $T1{\sim}2N0$ 유방암 환자 1,200명을 후향적으로 분석하여 유방보존치료와 유방절제술을 사이의 차이를 비교해 보았다. 결과: 분석에 포함된 1,174명의 환자 중 601명이(51.2%) 유방보존치료를 받았고 573명이(48.8%) 유방절제술을 받았다. 유방절제술을 받은 군에서 유의하게 종양의 크기가 컸고, 다발성(multicentricity), 에스트로겐 및 프로게스테론 수용체 음성 등의 인자가 더 많은 경향을 보였다. 유방보존치료 및 유방절제술을 받은 환자의 10년 생존율은 각각 91.96%와 91.01%였고(p=0.1274), 10년 무병생존율은 각각 80.48%와 84.95%(p=0.8795)로 유의한 차이를 보이지 않았다. 결론: 조기 유방암에서 유방보존치료 내지는 유방절제술을 받은 군 사이에 환자 특성의 차이는 일부 있었으나 생존율에서 유의한 차이를 보이지 않았다.

• Clinical and Experimental Reproductive Medicine
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• 제29권4호
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• pp.337-343
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• 2002

Objectives: To investigate the distribution of $ER{\alpha}$, $ER{\beta}$, c-fos and c-jun in the uterine myoma and myometrium in oder to know how the tamoxifen cause the growth of myoma. Methods: Myoma and myometrial tissue were obtained from the postmenopausal women treated with tamoxifen in the patients with breast cancer and in the premenopausal patients, who were undergoing myoma of uterus from 1998 through 2000. The espression of each gene was quantitated with quantitative RT-PCR. Results: The expression of $ER{\alpha}$ was slightly increased in the myoma than the myometrium in the proliferative phase, and was slightly decreased in the myometrium than the myoma in the secretory phase. However it was not significant statistically. In the postmemopausal women treated with tamoxifen, $ER{\alpha}$ was expressed in all myoma and myome1rial tissues and the expression was not statistically significant. The expression ofER~ was slightly increased in the myome1rium than the leiomyoma in the proliferative and secretory phase, but it was not significant statistically. In the postmemopausal women treated with tamoxifen, the expression of ER~ was significantly incresed in the myome1rium than the leiomyoma. The expression of c-fos was significantly increased in the myome1rium than the leiomyoma in the proliferative and secretory phase. In the postmemopausal women treated with tamoxifen, the expression of c-fos was slightly increased in the leiomyoma than the myomelrium, however, it was not statistically significant. Conclusion: Tamoxifen may cause the growth of leiomyoma by $ER{\alpha}$ with AP-l pathway reducing the counteraction of 6$ER{\beta}$ to $ER{\alpha}$.

• Clinical and Experimental Reproductive Medicine
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• 제34권4호
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• pp.275-283
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• 2007

목 적: 본 연구에서는 생리혈에 존재하는 탈락된 자궁내막조직에서의 자궁내막증 관련 유전자들의 발현 양상과 자궁내막증 병태생리와의 관련성을 살펴보고자 하였다. 연구방법: 자궁내막증으로 확진된 환자 (n=16)와 정상 대조군 (n=26)에서 생리주기 2$\sim$3일째 Wallace catheter로 채취한 생리혈로부터 탈락된 자궁내막조직을 분리하였다. 기존의 연구들에서 보고된 12종류의 자궁내막증 관련 유전자들의 mRNA 발현 양상을 semi-quantitative RT-PCR 방법으로 비교, 분석하였다. 결 과: 생리혈에서 분리한 탈락된 자궁내막조직은 조직학적 관찰을 통해 자궁내막조직임을 확인하였다. 총 12가지 종류의 자궁내막증 관련 유전자에 대한 RT-PCR 분석에서 telomerase, c-kit, aromatase등의 mRNA 발현이 관찰되지 않았다. 세포사멸 (apoptosis)과 관련성이 있는 fas, fas ligand, bcl-2, bax 유전자와 stem cell factor, ER-$\alpha$/$\beta$, endometriosis protein-I, secretory leukocyte protease inhibitor 등의 mRNA 발현 양상은 자궁내막증으로 확진된 환자군과 대조군에서 통계적으로 유의한 차이를 나타내지 않았다. 결 론: 결론적으로 자궁내막증과 관련된 다양한 유전자들의 발현 양상을 생리혈에 존재하는 탈락된 자궁내막조직에서 분석하였지만 의미성이 있는 유전자를 동정하지는 못하였다. 이는 자궁내막조직의 생리학적 특징인 생리주기에 따른 유전자 발현의 역동적인 변화와 관련이 있을 것으로 생각된다.

• 한국식품위생안전성학회지
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• 제21권4호
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• pp.197-203
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• 2006

Parabens are most wildly used in food, cosmetics and pharmaceutic products as preservatives caused of safety and cheap. we had examined that paraben had estrogenic activity through the in vivo and in vitro experiments in last year. We demonstrated that most of parabens(ethyl, butyl, propyl, isobutyl, isopropyl) increased significantly uterus weight as well as induced proliferation of MCF-7 cell and binding of estrogen receptor as endocrine disrupter compounds. In this study, we evaluated that whether parabens have effect on male reproductive system or not. the male rats were administrated parabens by oral injection then examined separation of preputial day for $PND23\simPND52$. As the results, most parabens delayed pubertal development compare to control group. The separation of preputial day of Butyl and Propyl parabens at high concentration were PND 44 days and PND 45days compared to control group as PND 40 days. Even though, parabens as endocrine disrupter wildly spread in food, cosmetics and pharmaceutic products, we didn't have the safe guideline. In abroad, they are re-evaluating safety assessment for parabens. In conclusion, parabens delayed pubertal development in juvenile parabens are consider as endocrine disrupter chemicals.