• Radiation Oncology Journal
• /
• 제26권1호
• /
• pp.45-55
• /
• 2008

목적: 45세 이하의 유방암 환자의 종양조직의 파라핀 블록을 조직미세배열법(Tissue Microarray, TMA)으로 만들어 에스트로겐 수용체(ER), 프로게스테론 수용체(PR), HER-2, COX-2 및 Survivin 등 5가지의 생체표지자의 발현상태와 상호관계, 환자의 치료 후 추적관찰 상태와 관련성을 분석하여 예후인자로서의 의의를 연구하는 데 있다. 대상 및 방법: 1994년 3월부터 2005년 8월까지 수술을 시행한 45세 이하의 유방암 환자 중에서 TMA 분석이 가능한 212명의 환자를 대상으로 하였다. 환자의 나이는 23세부터 45세까지로 중앙 나이가 39세이었으며 최소 추적관찰기간은 24개월, 중앙 추적 관찰기간은 60개월이었다. 45세 이하의 환자를 선택한 후 수술 조직표본을 찾아 HE 염색된 슬라이드를 통해 암 부위를 표시한 후 TMA 장비를 통해 미세조직배열을 만들었다. 그리고 다섯 가지 생체표지자에 대한 면역조직화학 염색을 시행하였으며 병리전문의가 판독하였다. 그리고 이 결과와 환자들의 연령, 병기, 림프절 전이, 수술방법, 다양한 약물요법과 가족력 등 여러 가지 인자와 환자의 추적 관찰 결과를 입력하여 예후인자들을 분석하였다. 결과: T 병기에 따른 환자 분포는 T1이 90명, T2가 101명으로 다수를 차지하였고 105명(49.5%)에서 액와 림프절의 전이가 있었다. 모든 환자의 5년 무병 생존율과 5년 생존율은 각각 82.3%, 90.4%이었으며 36명의 환자가 국소 재발이나 원격전이가 추적 관찰기간에 발생하였고 20명은 암과 관련하여 사망하였다. ER, PR, HER-2, COX-2, 그리고 survivin의 양성 발현비율은 각각 38.2%, 45.3%, 25.9%, 41.5%와 43.4%이었으며 종양의 크기, 나이, 림프절 전이의 여부, 호르몬 수용체의 상태, 그리고 HER-2의 상태가 무병 생존기간에 대한 단변량 분석상 중요한 예후인자 이었으며 생존율에 미치는 영향은 종양의 크기, 림프절의 전이, 호르몬 수용체, 그리고 HER-2의 발현이었다. COX-2나 survivin은 예후인자로서의 역할을 찾을 수 없었으나 HER-2와 COX-2가 동시에 발현되는 경우에 예후가 나쁜 경향을 관찰할 수 있었다. 다변량 분석상 오직 T-병기와 림프절의 전이 여부만이 중요한 예후 인자이었고 ER은 경계의 의미가 있었다. 결론: 45세 이하의 여성 유방암 환자에서 호르몬 수용체 상태와 HER-2는 예후인자이었고 COX-2와 survivin은 예후인자로서의 역할을 찾을 수 없었다.

• Journal of Microbiology and Biotechnology
• /
• 제30권2호
• /
• pp.178-186
• /
• 2020

Licorice (Glycyrrhiza uralensis) contains several compounds that have been reported to alleviate menopausal symptoms via interacting with estrogen receptors (ERs). The compounds exist mainly in the form of glycosides, which exhibit low bioavailability and function. To bioconvert liquiritin and isoliquiritin, the major estrogenic compounds, to the corresponding deglycosylated liquiritigenin and isoliquiritigenin, respectively, licorice was fermented with Monascus, which has been demonstrated to deglycosylate other substances. The contents of liquiritigenin and isoliquiritigenin in Monascus-fermented licorice increased by 10.46-fold (from 38.03 μM to 379.75 μM) and 12.50-fold (from 5.53 μM to 69.14 μM), respectively, compared with their contents in non-fermented licorice. Monascus-fermented licorice exhibited 82.5% of the ERβ binding activity of that observed in the positive control (17 β-estradiol), whereas the non-fermented licorice exhibited 54.1% of the binding activity in an in vivo ER binding assay. The increase in the ERβ binding activity was associated with increases in liquiritigenin and isoliquiritigenin contents. Liquiritigenin acts as a selective ligand for ERβ, which alleviates menopausal symptoms with fewer side effects, such as heart disease and hypertension, compared with a ligand for ERα. In addition, Monascus-fermented licorice contained 731 mg/kg of monacolin K, one of the metabolites produced by Monascus that reduces serum cholesterol. Therefore, Monascus-fermented licorice is a promising material for the prevention and treatment of menopausal syndrome with fewer side effects.

• Animal cells and systems
• /
• 제7권3호
• /
• pp.227-235
• /
• 2003

Bisphenol A (BPA), nonylphenol (NP), and 4-tert-octylphenol (OP) are known endocrine disrupting chemicals (EDCs) with estrogenic activity in fish. This study compared the effects of BPA, NP and OP on in vitro vitellogenin (VTG) synthesis in primary cultures of hepatocytes of the Chinese minnow Phoxinus oxycephalus. The VTG secreted into the culture medium was measured using enzyme-linked immunosorbent assay (ELISA), which we developed in this study using an antibody prepared from homogenates of Chinese minnow egg. VTG synthesis was induced by estradiol-17$\beta$ ($E_2$) and phenols (BPA, NP and OP) treatment. $E_2$ at concentrations of 10$^{-6}$ M or higher increased VTG levels significantly (P < 0.05). Exposure to 10^5\;M\;BPA\;or\;10^-4$M NP and OPinduced in vitro VTG synthesis (P < 0.01). However, $10^-3$ M BPA, NP or OP did not induce VTG synthesis. These results suggest that SPA has the highest estrogenic potential in Chinese minnow hepatocytes. Tamoxifen, an anti-estrogen, drastically blocked the production of VTG by phenols (BPA, NP and OP) suggesting that phenols (BPA, NP and OP) may act via binding to estrogen receptor (ER) in Chinese minnow hepatocytes.

• 대한한의학회지
• /
• 제43권3호
• /
• pp.79-93
• /
• 2022

Objectives: We investigated the isoflavone contained in SH003 and its fractions, and the effect of these components on the inhibition of breast cancer. Methods: The isoflavones in solvent fractions of SH003 extract were identified by UPLC-MS and its contents were quantified using HPLC analysis. The estrogenic activity of SH003 or fractions was assessed by ERE luciferase assay in estrogen receptor (ER)-positive MCF-7 cells. To test the breast cancer inhibitory effect, the cell viability was measured using an MTT assay. Results: In this study, we demonstrated that SH003 and fractions contain 4 isoflavones which are calycosin-7-β-D-glucoside, formononetin-7-β-D-glucoside, calycosin, and formononetin. Despite containing isoflavones, estrogen-dependent transcription activity was not altered by both SH003 and fractions. On the other hand, SH003 and fractions inhibited the cell viability of breast cancer. In addition, its isoflavone components also showed reduced cell viability in various breast cancer cells. Conclusions: Overall, the phytoestrogen included in SH003 and fractions did not influence the estrogenic activity, emphasizing the safety of SH003 and fractions in breast cancer treatment.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권4호
• /
• pp.1197-1201
• /
• 2012

Objective: To study the relationship between clinical pathologic characteristics, treatment modalities and prognostic factors in HER-2 (Human Epidermal growth factor Receptor-2) overexpressed breast carcinoma. Materials and Methods: Major clinico-pathological factors including therapeutic modalities and survival status of 371 breast cancer patients with HER2 over-expression, teated at Yantai Yuhuangding Hospital from March of 2002 to December of 2010 were retrospectively studied, with special attention focused on survival-related factors. Results: The median age of the total 371 patients in this study was 48 years at time of diagnosis, among which, the leading pathological type was infiltrating ductal carcinoma (92.5%); 62.8% presented with a primary tomor larger than 2 cm in diameter at diagnosis, 51.0% had axillary lymph node (ALN) metastases; ER (Estrogen receptor)/PR (Progesterone receptor) double negative occured in 52.8% of cases, and PCNA (proliferation cell nuclear antigen) (+++) was found in 55.1%. HER-2 overexpressed patients were usually in advanced stage when the diagnosis was made (72.8% at stages IIA~IIIC). The prognosis and survival were assessed in 259 patients with complete follow-up data. 5-year DFS (disease-free survival) and OS (overall survival) rate was 68.0% and 78.0% respectively. Univariate analysis revealed that age, tumor size, ALN metastases, LVSI (lymph-vascular space involvement), PCNA status, hormonal therapy, chemotherapy cycles, and HER-2 overexpression, correlated closely with the prognosis. ALN metastases, LVSI, PCNA status and chemotherapy cycles were independent predictors of survival. Conclusions: HER-2 overexpressed breast cancer has special clinical and pathological characteristics, with advanced clinical stages and high rate of ER/PR double negative. Lymph node metastases, LVSI, PCNA and chemotherapy cycles are independent predictors of prognosis.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권8호
• /
• pp.3681-3685
• /
• 2012

Background: In breast cancer, estrogen receptors have been demonstrated to interact with transcription factors to regulate target gene expression. However, high-throughput identification of the transcription regulation relationship between transcription factors and their target genes in response to estradiol is still in its infancy. Purpose: Thus, the objective of our study was to interpret the transcription regulation network of MCF7 breast cancer cells exposed to estradiol. Methods: In this work, GSE11352 microarray data were used to identify differentially expressed genes (DEGs). Results: Our results showed that the MYB (v-myb myeloblastosis viral oncogene homolog [avian]), PGR (progesterone receptor), and MYC (v-myc myelocytomatosis viral oncogene homolog [avian]) were hub nodes in our transcriptome network, which may interact with ER and, in turn, regulate target gene expression. MYB can up-regulate MCM3 (minichromosome maintenance 3) and MCM7 expression; PGR can suppress BCL2 (B-cell lymphoma 2) expression; MYC can inhibit TGFB2 (transforming growth factor, beta 2) expression. These genes are associated with breast cancer progression via cell cycling and the $TGF{\beta}$ signaling pathway. Conclusion: Analysis of transcriptional regulation may provide a better understanding of molecular mechanisms and clues to potential therapeutic targets in the treatment of breast cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권18호
• /
• pp.8135-8140
• /
• 2016

Background: Cell cycle regulatory proteins are suitable targets for cancer therapeutic development since genetic alterations in many cancers also affect the functions of these molecules. Strobilanthes crispus (S. crispus) is traditionally known for its potential benefits in treating various ailments. We recently reported that an active sub-fraction of S. crispus leaves (SCS) caused caspase-dependent apoptosis of human breast cancer MCF-7 and MDA-MB-231 cells. Materials and Methods: Considering the ability of SCS to also promote the activity of the antiestrogen, tamoxifen, we further examined the effect of SCS in modulating cell cycle progression and related proteins in MCF-7 and MDA-MB-231 cells alone and in combination with tamoxifen. Expression of cell cycle-related transcripts was analysed based on a previous microarray dataset. Results: SCS significantly caused G1 arrest of both types of cells, similar to tamoxifen and this was associated with modulation of cyclin D1, p21 and p53. In combination with tamoxifen, the anticancer effects involved downregulation of $ER{\alpha}$ protein in MCF-7 cells but appeared independent of an ER-mediated mechanism in MDA-MB-231 cells. Microarray data analysis confirmed the clinical relevance of the proteins studied. Conclusions: The current data suggest that SCS growth inhibitory effects are similar to that of the antiestrogen, tamoxifen, further supporting the previously demonstrated cytotoxic and apoptotic actions of both agents.

• Biomolecules & Therapeutics
• /
• 제20권3호
• /
• pp.313-319
• /
• 2012

In recent years, inhibition of HDACs has emerged as a potential strategy to reverse aberrant epigenetic changes associated with cancer, and several classes of HDAC inhibitors have been found to have potent and specific anticancer activities in preclinical studies. But their precise mechanism of action has not been elucidated. In this study, a novel synthetic inhibitor of HDAC, 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide [IN-2001] was examined for its antitumor activity and the underlying molecular mechanisms of any such activity on human breast cancer cell lines. IN-2001 effectively inhibited cellular HDAC activity ($IC_{50}$ = 0.585 nM) inMDA-MB-231 human breast cancer cells. IN-2001 caused a significant dose-dependent inhibition of cell proliferation in estrogen receptor (ER) negative MDA-MB-231human breast cancer cells. Cell cycle analysis revealed that the growth inhibitory effects of IN-2001 might be attributed to cell cycle arrest at $G_0/G_1$ and/or $G_2$/Mphase and subsequent apoptosis in human breast cancer cells. These events are accompanied by modulating several cell cycle and apoptosis regulatory genes such as CDK inhibitors $p21^{WAF1}$ and $p27^{KIP1}$ cyclin D1, and other tumor suppressor genes such as cyclin D2. Collectively, IN-2001 inhibited cell proliferation and induced apoptosis in human breast cancer cells and these findings may provide new therapeutic approaches, combination of antiestrogen together with a HDAC inhibitor, in the hormonal therapy-resistant ER-negative breast cancers. In summary, our data suggest that this histone deacetylase inhibitor, IN-2001, is a novel promising therapeutic agent with potent antitumor effects against human breast cancers.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권11호
• /
• pp.4507-4511
• /
• 2014

Background: Breast cancer is a heterogeneous disease comprising of distinct biological subtypes with many targeted prognostic biomarkers having therapeutic implications. However, no specific targeted therapy for triple negative breast cancer has been discovered to date and hence further research is needed. Aim: The aim and objectives of the present study were to examine the prevalence of triple negative breast cancer (TNBC) in North-East India and to compare the clinicopathological parameters in two study groups defined by immunohistochemistry (IHC) - "TNBC" and "Others". Materials and Methods: We carried out a retrospective study in a cohort of 972 patients diagnosed with invasive breast carcinoma in the Department of Pathology, Dr. B. Borooah Cancer Institute, a Regional Cancer Centre for treatment and research, Guwahati, for a period of 3 years and 10 months from January 2010 to October 2013. Based on IHC findings, patients were divided into two groups - "TNBC" and "Others". All relevant clinicopathological parameters were compared in both. TNBC were defined as those that were estrogen receptor (ER), progesterone receptor (PR), and HER2/neu negative while those positive for any of these markers were defined as "Others". Results: In this study, out of total 972 cases 31.9% (310 cases) were defined as TNBC and 662 cases (68.1%) as "Others" based on IHC markers. Compared to the "Others" category, TNBC presented at an early age (mean 40 years), were associated with high grade large tumours and high rate of node positivity, IDC NOS being the most common histological subtype in TNBC. Conclusions: TNBC accounts for a significant portion of breast cancers in this part of India and commonly present at younger age and tend to be large high grade tumours.

• Asian-Australasian Journal of Animal Sciences
• /
• 제22권11호
• /
• pp.1495-1503
• /
• 2009

This experiment was conducted to determine the effect of dietary supplementation with BCAA (branched-chain amino acids: leucine, isoleucine and valine) on improving the growth of rats in a malnutritional IUGR (Intrauterine Growth Retardation) model, which was established by feeding restriction. In the experimental treatment, rats were fed purified diets supplemented with BCAA (mixed) during the whole gestation period, while arginine and alanine supplementation were set as the positive and negative control group, respectively. The results showed that, compared to the effect of alanine, BCAA reversed IUGR by increasing the fetus weights by 18.4% and placental weights by 18.0% while fetal numbers were statistically increased. Analysis of gene and protein expression revealed that BCAA treatment increased embryonic liver IGF-I expression; the uterus expressed higher levels of estrogen receptor-$\alpha$ (ER-$\alpha$) and progesterone receptor (PR), and the placenta expressed higher levels of IGF-II. Amino acid analysis of dam plasma revealed that BCAA supplementation effectively enhanced the plasma BCAA levels caused by the feed restriction. BCAA also enhanced the embryonic liver gluconeogenesis by augmenting the expression of two key enzymes, namely fructose-1,6-biphosphatase (FBP) and phosphoenolpyruvate carboxykinase (PEPCK). In conclusion, supplementation of BCAA increased litter size, embryonic weight and litter embryonic weight by improving the dam uterus and placental functions as well as increasing gluconeogenesis in the embryonic liver, which further provided energy to enhance the embryonic growth.