• Parasites, Hosts and Diseases
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• 제54권1호
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• pp.9-14
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• 2016

Tamoxifen is an antagonist of the estrogen receptor and currently used for the treatment of breast cancer. The current treatment of cutaneous leishmaniasis with pentavalent antimony compounds is not satisfactory. Therefore, in this study, due to its antileishmanial activity, effects of tamoxifen on the growth of promastigotes and amastigotes of Leishmania major Iranian strain were evaluated in vitro. Promastigotes and amastigotes were treated with different concentrations (1, 5, 10, 20, and $50{\mu}g/ml$) and time periods (24, 48, and 72 hr) of tamoxifen. After tamoxifen treatment, MTT assay (3-[4,5-dimethylthiazol-2-yl]-2,5 biphenyl tetrazolium bromide assay) was used to determine the percentage of live parasites and Graph Pad Prism software to calculate $IC_{50}$. Flow cytometry was applied to investigate the induction of tamoxifen-induced apoptosis in promastigotes. The half maximal inhibitory concentration ($IC_{50}$) of tamoxifen on promastigotes was $2.6{\mu}g/ml$ after 24 hr treatment. Flow cytometry analysis showed that tamoxifen induced early and late apoptosis in Leishmania promastigotes. While after 48 hr in control group the apoptosis was 2.0%, the $50{\mu}g/L$ concentration of tamoxifen increased it to 59.7%. Based on the in vitro antileishmanial effect, tamoxifen might be used for leishmaniasis treatment; however, further researches on in vivo effects of tamoxifen in animal models are needed.

• Journal of Gastric Cancer
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• 제20권1호
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• pp.106-114
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• 2020

Breast metastases of extramammary malignant neoplasms are rare, with an incidence of 0.3%-2.7% among all malignant mammary tumors. Breast metastases from gastric carcinoma are very rare (<0.1%), and this event is even rarer during pregnancy. Herein, we describe a 39-year-old Caucasian woman with a history of an Epstein-Barr virus-associated gastric carcinoma (EBVaGC) that was characterized by prominent tumor infiltrating lymphocytes. Three years after undergoing radical surgery, the patient developed bilateral breast nodules during her pregnancy. A breast biopsy was performed, and histology confirmed a diagnosis of EBVaGC; tumor cells showed positivity for cytokeratin 8/18 and E-cadherin, and negativity for cytokeratin 7, cytokeratin 20, cytokeratin 5/6, caudal type homebox 2, androgen receptor, mammaglobin, gross cystic disease fluid protein-15, and estrogen and progesterone receptors. We also discuss the main diagnostic pitfalls. To our knowledge, this is the first report of an EBVaGC with lymphoid stroma that developed breast metastases during pregnancy.

• Environmental Analysis Health and Toxicology
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• 제27권
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• pp.10.1-10.7
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• 2012

Objectives: In recent years, a number of structurally diverse Histone deacetylase (HDAC) inhibitors have been identified and these HDAC inhibitors induce growth arrest, differentiation and/or apoptosis of cancer cells in vitro and in vivo. This study aimed at investigating the antitumor activity of newly synthesized HDAC inhibitor, 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide (IN-2001) using human breast cancer cells. Methods: We have synthesized a new HDAC inhibitor, IN-2001, and cell proliferation inhibition assay with this chemical in estrogen receptor-positive human breast cancer MCF-7 cells. Cell cycle analysis on MCF-7 cells treated with IN-2001 was carried out by flow cytometry and gene expression was measured by RT-PCR. Results: In MCF-7 cells IN-2001 showed remarkable anti-proliferative effects in a dose- and time-dependent manner. In MCF-7 cells, IN-2001 showed a more potent growth inhibitory effect than that of suberoylanilide hydroxamic acid. These growth inhibitory effects were related to the cell cycle arrest and induction of apoptosis. IN-2001 showed accumulation of cells at $G_2$/M phase and of the sub-$G_1$ population in a time-dependent manner, representing apoptotic cells. IN-2001-mediated cell cycle arrest was associated with HDAC inhibitor-mediated induction of CDK inhibitor expression. In MCF-7 cells, IN-2001 significantly increased $p21^{WAF1}$ expression. Conclusions: In summary, cyclin-dependent kinase (CDK) induced growth inhibition, possibly through modulation of cell cycle and apoptosis regulatory proteins, such as CDK inhibitors, and cyclins. Taken together, these results provide an insight into the utility of HDAC inhibitors as a novel chemotherapeutic regime for hormone-sensitive and insensitive breast cancer.

• Toxicological Research
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• 제21권1호
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• pp.31-37
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• 2005

The inhibitory activity against bisphenol-A (BPA), one of well-known endocrine disrupters was examined with the water extracts prepared from the Stem Bark of Syringa velutina (SBS). In this study, we have investigated the effect of SBS on the toxicity caused by BPA in human breast cancer cell line, MCF-7 cells and immature Sprague-Dawley rats. In the estrogen receptor-mediated proliferation assay using MCF-7 cells, BPA (16 ng/ml) induced the cell proliferation, but the water extract of SBS inhibited BPA-induced cell proliferation in a dose-dependent manner. These results are associated with PARP degradation and specific cleavage of anti-apoptotic protein Bcl-2 of apoptotic regulatory factors. Additionally, the BPA (400 mg/100 g) significantly induced the increase of the uterine and virginal weights, while SBS (50 mg/100 g) showed the inhibitory action against BPA, i.e. caused the increase of estrogen-related organ weights in immature rat uterotrophic assay. Taken together, the present data suggest that SBS may have anti-toxicity activities against BPA in vitro and in vivo systems. SBS may be capable of inhibiting adverse effects of BPA such as reproductive disorder.

• 한국미생물·생명공학회지
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• 제39권3호
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• pp.224-237
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• 2011

대두 이소플라본 성분의 유방암 항암성과 다양한 폐경기 증상의 완화 효능을 분석하고자 유방밀도와 안면홍조현상의 억제능을 생체 마커로 설정하였다. 중재 유형으로 대두, 적클로버, 승마 등에서 정제된 이소플라본과 대두의 조추출액을 설정하여 지난 15년간의 관련 논문을 색인, 40여 편의 중재논문을 선별하였다. 이소플라본의 효과는 유방영역, 밀집, 비밀집 영역, 홍조의 심화도, 발생 빈도, 혈관질환성 등을 종속변수로 설정, 복용량, 복용기간, 복용시기, 폐경 여부 등의 요인에 따른 항암 효과를 비교분석하였다. 그 결과 중재유형별로 유방밀도와 안면홍조의 억제효능에서 전자는 대두 추출물에서, 후자는 정제된 이소플라본에서 현저하게 강한 효능이 나타났다. 종속변수로써 유방밀도는 밀집영역과 음영백분율에서는 양성적 효능이 인정되었고, 안면홍조에서는 홍조의 심화도에 비해 발생빈도가 현저히 억제되었다. 유방 밀도와 안면홍조에 강한 억제 효능이, 복용량에서는 50 mg/일 이상 100 mg/일 미만, 복용기간은 1년 정도가 가장 효율성이 높은 노출기간으로 판정되었다. 특히 폐경 전이 폐경후보다 유방밀도와 안면홍조의 억제효과가 더 강하게 나타났다. 이상의 결과 포괄적인 메타분석에서 유방밀도는 이소플라본에 의해 2%가 억제되어 효능이 약하였지만 안면홍조는 23%의 강한 억제효능이 있는 것으로 해석되었다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권2호
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• pp.459-462
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• 2012

Expression of estrogen-receptor (ER), progesterone-receptor (PR) and HER-2 has recently been linked with various breast cancer subtypes identified by gene microarray. This study aimed to document breast cancer subtypes based on ER, PR and HER-2 status in Thai women, where expression of these subtypes may not be similar to those evident in Western women. During 2009 to 2010, histological findings from 324 invasive ductal carcinomas (IDC) at Siriraj Hospital were studied. Various subtypes of IDC were identified according to expression of ER, PR and HER-2: luminal-A (ER+;PR+/-;HER-2-), luminal-B (ER+;PR+/-;HER-2 +), HER-2 (ER-;PR- ;HER-2+) and basal-like (ER-;PR-;HER-2-). As well, associations of tumor size, tumor grade, nodal status, angiolymphatic invasion (ALI), multicentricity and multifocality with different breast cancer subtypes were studied. Of 324 IDCs, 143 (44.1%), 147 (45.4%), 15 (4.6%) and 12 (3.7%) were T1, T2, T3 and T4, respectively. Most tumors were grade 2 (54.9%) and had no nodal involvement (53.4%). According to ER, PR and HER-2 status, 192 (59.3%), 40 (12.3%), 43 (13.3%) and 49 (15.1%) tumors were luminal-A, luminal-B, HER-2 and basal-like subtypes. HER-2 subtype presented with large tumor (p=0.04, ANOVA). Luminal-A IDC was associated with single foci (p<0.01, ${\chi}^2$). HER-2 and basal-like subtypes were likely to have high tumor grade (p<0.01, ${\chi}^2$). In addition, HER-2 subtype had higher number of nodal involvement (p=0.048, ${\chi}^2$). In conclusion, the luminal-A subtype accounted for the majority of IDCs in Thai women. Percentages of HER-2 and basal-like IDCs were high, compared with a recent study from the USA. The HER-2 subtype was related with high nodal invasion. The findings may highlight biological differences between IDCs occurring in Asian and Western women.

• Investigative Magnetic Resonance Imaging
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• 제23권2호
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• pp.125-135
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• 2019

Purpose: The purpose of this study was to evaluate dynamic contrast-enhanced breast magnetic resonance imaging (DCE-MRI), and diffusion-weighted imaging (DWI) variables, for axillary lymph node (ALN) metastasis in the early stage of breast cancer. Materials and Methods: January 2011-April 2015, 787 patients with early stage of breast cancer were retrospectively reviewed. Only cases of invasive ductal carcinoma, were included in the patient population. Among them, 240 patients who underwent 3.0-T DCE-MRI, including DWI with b value 0 and $800s/mm^2$ were enrolled. MRI variables (adjacent vessel sign, whole-breast vascularity, initial enhancement pattern, quantitative kinetic parameters, signal enhancement ratio (SER), tumor apparent diffusion coefficient (ADC), peritumoral ADC, and peritumor-tumor ADC ratio) clinico-pathologic variables (age, T stage, multifocality, extensive intraductal carcinoma component (EIC), estrogen receptor, progesterone receptor, HER-2 status, Ki-67, molecular subtype, histologic grade, and nuclear grade) were compared between patients with axillary lymph node metastasis and those with no lymph node metastasis. Multivariate regression analysis was performed, to determine independent variables associated with ALN metastasis, and the area under the receiver operating characteristic curve (AUC), for predicting ALN metastasis was analyzed, for those variables. Results: On breast MRI, moderate or prominent ipsilateral whole-breast vascularity (moderate, odds ratio [OR] 3.45, 95% confidence interval [CI] 1.28-9.51 vs. prominent, OR = 15.59, 95% CI 2.52-96.46), SER (OR = 1.68, 95% CI 1.09-2.59), and peritumor-tumor ADC ratio (OR = 6.77, 95% CI 2.41-18.99), were independently associated with ALN metastasis. Among clinico-pathologic variables, HER-2 positivity was independently associated, with ALN metastasis (OR = 23.71, 95% CI 10.50-53.54). The AUC for combining selected MRI variables and clinico-pathologic variables, was higher than that of clinico-pathologic variables (P < 0.05). Conclusion: SER, moderate or prominent increased whole breast vascularity, and peritumor-tumor ADC ratio on breast MRI, are valuable in predicting ALN metastasis, in patients with early stage of breast cancer.

• 대한영상의학회지
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• 제81권2호
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• pp.395-408
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• 2020

목적 유방암 일차치료 후 조기 재발 예측에 도움이 되는 임상병리학적 인자 및 원발암의 영상의학적 특징을 알아보고자 하였다. 대상과 방법 본원에서 2010년 1월부터 2014년 12월까지 유방 보존 수술 및 보조요법 치료 후 추적관찰을 받은 480명을 대상으로 하였다. 일차치료 완결 후 3년 이내 재발한 경우를 조기재발으로 정의하고, 이와 관련된 임상병리학적 및 영상의학적 예측인자를 알아보기 위해 단변량 및 다변량 로지스틱 회귀분석을 시행하였다. 결과 단변량 분석에서 임상병리학적 인자 중 높은 종양 병기(p = 0.021), 고등급 조직학적 분화도(p < 0.001), estrogen receptor 수용체 음성(p = 0.002), Ki-67 과발현(p = 0.017), 삼중음성유방 아형(p = 0.019)과, 영상 소견 중 유방암의 다초점성(p < 0.001), 도플러 검사에서 테두리 혈류(p = 0.012), 자기공명영상에서 테두리 조영증강(p < 0.001)이 조기 재발과 유의한 연관성을 보였다. 다변량 분석에서 원발암의 높은 종양 병기[odds ratio (이하 OR) = 3.47, 95% confidence interval (이하 CI) 1.12~10.73, p = 0.031]와 도플러 검사에서 테두리 혈류 (OR = 3.32, 95% CI 1.38~8.02,p = 0.008)가 조기 재발과 관련된 독립적인 예측인자였다. 결론 유방암 치료 전 도플러 검사에서 원발암의 테두리 혈류 소견은 유방암의 일차치료 후 조기 재발의 독립적인 영상의학적 예측인자이다.

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

• Clinical and Experimental Reproductive Medicine
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• 제27권2호
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• pp.117-131
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• 2000

Objectives: To develop a new immunohistochemical marker system for supplementation of the Noyes histological classification of the endometrium in women of child bearing age with regular menstrual cycles, and to employ this system to evaluate pathologic factors involved in endometriosis, and thus to ascertain if it is useful in diagnosis. Materials and Methods: Endometrial biopsies were sampled from the posterior fundus of 41 (24 proliferative phases, 17 secretory phases) women with regular menstrual cycles (28-32 days), and each sample was immunohistochemically stained according to Noyes et al (1975) for determination of expression for estrogen receptor (ER), progesterone receptor (PR), integrin ${\alpha}_1$, ${\alpha}_4$, ${\beta}_3$, COX-1 and COX-2. Then, the PR, integrin ${\beta}_3$ and COX-2 which were clearly expressed in the luteal phase was with endometrial samples were obtained from 20 cases of normal patients (group 1) and 25 cases with endometriosis (group 2) after confirming the day of ovulation by sex steroid level measurements 7-8 days after ovulation Results: In the regular menstruation group the expression of ER showed a tendency to be increased in the proliferative phase and decreased in the secretory phase, and was the highest in the proliferative phase. However, PR in the stromal cells showed no change in the entire menstrual cycle while in the epithelial cells, PR reached a peak in the late proliferative phase and was almost absent in the secretory phase. Integrin (${\alpha}_1$, ${\alpha}_4$, and ${\beta}_3$ expression in the epithelial cells was absent in the proliferative phase but ${\alpha}_1$ was strongly expressed starting from the early secretory phase into the entire secretory phase. ${\alpha}_4$ was expressed strongly in the early and mid secretory phases and disappeared in the late proliferative phase, while ${\beta}_3$ appeared after the mid secretory phase and continued to be expressed until the late secretory phase. Expression in the stromal cells was weak overall and did not show any cyclic pattern. COX-1 expression was shown as a cyclic pattern in the stromal and epithelial cells and was particularly strongly expressed in the mid secretory phase of epithelial cells, and in the mid secretory and menstruation phase of stromal cells. In the endometrial epithelial cells there was strong expression during the entire cycle with stronger expression in the secretory phase compared to the prolferative phase. COX-2 was clearly expressed in the late proliferative, early and mid secretory phases in the stromal cells. No expression was observed in the proliferative phase of the epithelial cells, but which began to appear in the early secretory phase reaching a significant pattern from the mid secretory phase onwards. There was almost no expression in the stromal cells. In the cases with endometriosis showing normal endometrial maturation according to the Noyes classification, PR expression was increased while Integrin-${\beta}_3$의 expression was significantly decreased compared to the normal group. Also, COX-2 expression was slightly decreased in the stromal cells of patients with endometriosis while it was significantly increased in the stromal cells. Conclusion: Immunohistochemical markers can supplement the original Noyes classification of histological endometrial dating and therefore ascertain existing pathologic conditions. Particularly for patients with endometriosis with normally mature endometrial cells, changes in COX-2 and integrin expression patterns may assist in elucidating pathophysiologic mechanisms and therefore aid in the diagnosis of abnormal implantation conditions, and consequently determine a treatment modality.