• Journal of Ginseng Research
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• 제46권4호
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• pp.526-535
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• 2022

Background: During the pathogenesis of tendinopathy, the chronic inflammation caused by the injury and apoptosis leads to the generation of scars. Ginsenoside Rg1 (Rg1) is extracted from ginseng and has anti-inflammatory effects. Rg1 is a unique phytoestrogen that can activate the estrogen response element. This research aimed to explore whether Rg1 can function in the process of tendon repair through the estrogen receptor. Methods: In this research, the effects of Rg1 were evaluated in tenocytes and in a rat model of Achilles tendinitis (AT). Protein levels were shown by western blotting. qRT-PCR was employed for evaluating mRNA levels. Cell proliferation was evaluated through EdU assay and cell migration was evaluated by transwell assay and scratch test assay. Results: Rg1 up-regulated the expression of matrix-related factors and function of tendon in AT rat model. Rg1 reduced early inflammatory response and apoptosis in the tendon tissue of AT rat model. Rg1 promoted tenocyte migration and proliferation. The effects of Rg1 on tenocytes were inhibited by ICI182780. Rg1 activates the insulin-like growth factor-I receptor (IGF1R) and MAPK signaling pathway. Conclusion: Rg1 promotes injured tendon healing in AT rat model through IGF1R and MAPK signaling pathway activation.

• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1187-1192
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• 2014

Background: To correlate breast cancer subtypes with prognostic factors, microvessel density (MVD), vascular endothelial growth factor (VEGF) expression and clinical features. Materials and Methods: One hundred cases of primary breast carcinoma were classified using biomarkers on tissue microarray as: luminal A [estrogen receptor (ER)+, HER2-, $Ki-67{\leq}14%$], luminal B [ER+, HER2+ or ER+, HER2-, Ki-67>14%], HER2, triple negative basal-like (TNB) [any basal cytokeratins (CKs, 5, 14, 17) and/or endothelial growth factor receptor (EGFR) expression], and TN without such markers [TNN, null], and assessed for p53, vimentin, VEGF and CD31 immunoperoxidase. Results: Of the 100 cases (mean age, 51 years; mean tumor size, 3.2cm; 56% with nodal metastasis; 89 invasive ductal carcinomas, not otherwise specified, 4 invasive lobular carcinomas, 3 metaplastic carcinomas, and 4 other types) there were 39 luminal A, 18 luminal B, 18 HER2, 15 TNB and 10 TNN. The positivities of basal-like markers in the basal-like subtype were 78.3% for CK5, 40% for CK14, 20% for CK17, 46.7% for EGFR. There was no significant difference in age distribution, tumor size, degree of tubular formation, pleomorphism, lymphovascular invasion, nodal metastasis, MVD, VEGF expression and survival among subgroups. TNs demonstrated significantly higher tumor grade, mitotic count, Ki-67 index, p53 and vimentin and decreased overall survival compared with nonTN. Conclusions: The distribution of breast cancer subtypes in this study was similar to other Asian countries with a high prevalence of TN. The high grade character of TN was confirmed and CK5 expression was found to be common in our basal-like subtype. No significant elevation of MVD or VEGF expression was apparent.

• 대한임상검사과학회지
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• 제50권4호
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• pp.449-456
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• 2018

자궁경부암은 세계적으로 여성에서 네번째로 많이 진단되는 암이다. 개발 지수가 낮은 개발도상국이나 후진국에서는 자궁경부암의 발생률과 사망률이 훨씬 심각하다. 따라서 더 나은 진단법과 치료법이 시급하다. 인유두종바이러스가 자궁경부암 발생의 주요 원인으로 알려진 이후로 바이러스에 대한 검사가 세포검사 조직검사와 함께 자궁경부암을 진단하는데 일상적으로 쓰이고 있다. 하지만, HPV 검사에서 음성을 보이는 환자가 자궁경부암으로 발전하는 사례가 계속해서 발견되고 있다. 본 연구에서는 HPV 외에 자궁경부암의 원인으로 생각되는 인자들에 대해 분석하였다. 그 중에서도 에스트로겐 수용체 알파의 mRNA 발현양을 실시간 역전사 중합효소 연쇄반응을 통해 분석하였다. 에스트로겐 수용체 알파에 대해서는 예전부터 자궁내막을 성숙시키면서 동시에 자궁경부암의 발암 기전에 연관이 있을 것이라는 추측이 있었는데, 본 연구에서는 이에 대해 임상검체를 통해 양적 분석을 진행하였다. ROC 곡선을 바탕으로, 85%의 민감도와 75%의 특이도를 확인할 수 있었는데, 이 값은 기존의 HPV 검사법보다 유사하거나 더 높은 값이었다. 나이, 병변의 심한 정도 등을 포함한 임상 정보를 바탕으로 회귀 분석한 결과 폐경 여부와 에스트로겐 수용체 알파의 발현양이 높은 연관성을 확인하였다. 본 연구는 예비 연구의 일종으로, 추후 연구에서 가능성이 확인된 호르몬과 폐경에 관련된 유전자를 대상으로 더 많은 검체로 분석해야 할 것이다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10277-10280
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• 2015

Background and Aim: Breast cancer (BC) is a heterogeneous disease and cell proliferation markers may help to identify subtypes of clinical interest. We here analyzed the correlation between cell proliferation determined by Ki67 and HG in BC patients undergoing preoperative chemotherapy (PCT). Materials and Methods: We obtained clinical/pathological data from patients with invasive BC treated at our institution from 1999 until 2012. Expression of estrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor type 2 (HER2) and Ki67 were determined by immuno-histochemistry (IHC). Clinicopathological subtypes were defined as: Luminal A, ER and/or PR positive, HER2 negative, HG 1 or 2; Luminal B, ER and/or PR positive, HER2 negative or positive and/or HG 3; triple negative (TN), ER, PR and HER2 negative independent of HG; HER2 positive, ER, PR negative and HER2 positive, independent of HG. By using Ki67, a value of 14% separated Luminal A and B tumors, independently of the histological grade. We analyzed correlations between Ki67 and HG, to define BC subtypes and their predictive value for response to PCT. Results: 1,560 BC patients were treated in the period, 147 receiving PCT (9.5%). Some 57 had sufficient clinicopathological information to be included in the study. Median age was 52 years (26-72), with 87.7% invasive ductal carcinomas (n=50). We performed IHC for Ki67 in 40 core biopsies and 50 surgical biopsies, 37 paired samples with Ki67 before and after chemotherapy being available. There was no significant correlation between Ki67 and HG (p=0.237), both categorizing patients into different subtypes. In most cases Ki67 decreased after PCT (65.8%). Only 3 patients had pathologic complete response (cPR). Conclusions: In our experience we did not find associations between Ki67 and HG. Determination of clinicopathological luminal subtypes differs by using Ki67 or HG.

• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1381-1385
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• 2014

Background: The prognostic value of the Ki67 expression level is yet unclear in breast cancer. The aim of this study was to investigate the association between Ki67 expression levels and prognostic factors such as grade, Her2 and hormone receptor expression status in breast cancers. Materials and Methods: Clinical and pathological features of the patients with breast cancer were retreived from the hospital records. Results: In this study, 163 patients with breast cancer were analyzed, with a mean age of $53.4{\pm}12.2$ years. Median Ki67 positivity was 20% and Ki67-high tumors were significantly associated with high grade (p<0.001), lymphovascular invasion (p=0.001), estrogen receptor (ER) negativity (p=0.035), Her2 positivity (p=0.001), advanced stage (p<0.001) and lymph node positivity (p<0.003). Lower Ki67 levels were significantly associated with longer median relapse-free and overall survival compared to those of higher Ki67 levels. Conclusions: High Ki67 expression is associated with ER negativity, Her2 positivity, higher grade and axillary lymph node involvement in breast cancers. The level of Ki67 expression is a prognostic factor predicting relapse-free and overall survival in breast cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.267-274
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• 2013

The impact of income and education level on the clinical and pathologic characteristics, implementation of clinical breast examination (CBE), and treatment patterns of a small population of Chinese female breast cancer patients was studeied in order to provide a theoretical basis and statistical reference for further nationwide research. We included 484 pathologically confirmed female primary breast cancer inpatients of the First Affiliated Hospital of Medical College of Xi'an Jiaotong University from February 2003 to January 2004. All cases were reviewed and relevant information was collected using a designed case report form (CRF). Chisquare tests, rank-sum tests, and Fisher's exact tests were used in the analysis. Our analysis showed that: (1) women in different occupation groups had significant differences in tumor size, pre-operative mammography, surgical options, post-operative estrogen receptor (ER), progestin receptor (PR) and human epidermal growth factor receptor 2 (Her2) status, and post-operative radiotherapy and chemotherapy (P < 0.05); and (2) women with different education levels had statistically significant differences in tumor size, post-operative ER, PR and Her2 status, and post-operative chemotherapy, radiotherapy, and endocrine therapy (P < 0.05). In Xi'an, China, women in low-income occupations or with low education levels are more likely to have advanced tumor stages at presentation, lower implementation rate of clinical breast examination, and less treatment.

• 대한의생명과학회지
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• 제24권1호
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• pp.9-14
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• 2018

Ki-67 has been widely performed and become an important biomarker in worldwide clinics, but the standard cut off value of Ki-67 index in breast cancer is still controversy. The objective study was to understand the Ki-67 in breast cancer subtypes and to investigate relative risk of breast cancer subtypes according to Ki-67 cut off value in Korean breast cancer. Immunohistochemical staining (IHC) for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 index was examined from 123 breast cancer patients. Ki-67 index was significantly overexpressed in PR, ER, and HER2 hormone negative groups. Ki-67 index in Triple negative and HER2 subtypes was shown significantly higher than that in Luminal A and Luminal B subtype. Then, we compared the relative risk of each subtype according to 14% and 20% Ki-67 cut off value, which were applied in most clinics. Especially, 20% Ki-67 cut off value in HER2 and Triple negative subtypes was shown 8.41 fold and 2.83 fold higher relative risk than this in Luminal A subtype. Moreover, Ki-67 index in HER2 2+ or 3+ status showed significantly overexpressed than this in HER2 1+ status. At the 20% Ki-67 cut off value, HER2 1+ or 2+ status and 3+ status showed significant difference. Therefore, the 20% Ki-67 cut off value will be useful as a precise prognostic management and helpful for interpreting diverse outcomes of other subtypes in breast cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• 제16권17호
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• pp.7819-7824
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• 2015

Purpose: To subtype breast cancer (BC) in Saudi women according to the recent molecular classification and to correlate these subtypes with available clinicopathological parameters. Materials and Methods: Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (Her2/neu) immunostaining was semi-quantitatively assessed to define molecular subtypes of luminal A and B, HER-2 and triple negative (basal-like) in BC paraffin embedded sections from 115 Saudi female patients diagnosed between 2005 to 2015 at the Department of Pathology, King Fahd Hospital, Almadinah, Saudi Arabia. Results: The most common subtypes were luminal A (47%), followed by luminal B (27.8%) and basal like subtypes (18.3%), whereas HER-2 was the least common subtype (6.9%). Luminal A was predominantly found in the old age group, with low tumor grade (p<0.001) and small tumor size, whereas HER-2 and basal-like subtypes were significantly associated with young age, high tumor grade, lymph node metastasis and lymphovascular invasion (p<0.03, 0.004, 0.05 and 0.04 respectively). All subtypes showed advanced clinical stage at the time of presentation. Conclusions: Molecular subtypes of Saudi BC patients in Almadinah region are consistent with most of the worldwide subtyping. The biological behaviour of each molecular subtype could be expected based on its characteristic clinicopathological features. Along with other prognostic indicators, molecular subtyping would be helpful in predicting prognosis and management of our BC patients. We recommend screening and early diagnosis of BC in our population.

• Asian Pacific Journal of Cancer Prevention
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• 제16권12호
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• pp.4863-4867
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• 2015

Background: Triple negative breast cancer (TNBC), characterized as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 Her2 negative and accounting for 10-17% of all breast carcinomas, is only partially responsive to chemotherapy and suffers from a lack of clinically established targeted therapies. The aim of the current study was to evaluate the patterns of treatment and clinicopathology figures in Kurdish patients with triple-negative breast cancer, and to compare these to other reports. Materials and Methods: Between 2001 and 2014, 950 breast cancer patients were referred to our clinic. There were 74 female patients with TNBC, including 70 patients was invasive ductal carcinoma entered into our study. ER and PR positivity was defined as positive immunohistochemical staining in more than 10% of tumor cells. Immunohistochemistry assay with anti-HER2 antibodies was used to identify HER negative (0 and 1+) or positive (2+ and 3+). HER2 gene amplification was determined by fluorescent in situ hybridization (FISH). Overall survival (OS) was plotted with GraphPad Prism 5 Software using Kaplan-Meier and log-rank tests for comparison of results. Results: The mean age in the first diagnosis for 70 patients with triple TNBC and invasive ductal carcinoma was 49.6 years that range of age was 27-82 years. All of the patients were female. Of 70 patients, 23 patients had metastasis. Thirty-two patients (45.7%) were treated with tamoxifen and 39 (55.7%) with radiotherapy. Three-year, 5-year and 10-year OS rates for all patients were 82%, 72% and 64%, respectively. Conclusions: The OS in our West Iran TNBC patients is less than reported elsewhere. However, treatment with combination of tamoxifen plus radiation increases the OS and reduces the mortality rate.

• 생명과학회지
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• 제32권3호
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• pp.256-262
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• 2022

옥시스테롤은 담즙산 합성 동안 일련의 효소 반응에 의해 생성된 콜레스테롤의 산화물로써, 콜레스테롤과 유사하게 세포내 영역으로 빠르게 이동하여 면역 세포 반응, 지질 대사 및 콜레스테롤 항상성과 같은 다양한 세포 과정을 조절한다. 글루코코르티코이드 수용체(GR), 에스트로겐 수용체(ER) 및 간 X 수용체(LXR)와 같은 종류의 핵 수용체는 여러 조직에서 옥시스테롤에 의해 조절될 수 있다. 가장 풍부한 옥시스테롤인 27-하이드록시콜레스테롤(27-OHC)은 조직 특이적 방식에 의해 에스트로겐 수용체 활성을 활성화하거나 억제하기 때문에 선택적 에스트로겐 수용체 조절자로 규명되었다. 특히 27-하이드록시콜레스테롤이 동맥 경화증 플라크에서 많이 발견되고 대식세포가 거품 세포로 변형되는 것을 가속화하기 때문에 동맥 경화증 발병에 기여하는 것이 분명해 보이나, 다른 연구들에서는 27-하이드록시콜레스테롤이 간 및 지방 조직을 포함한 다양한 대사 기관에 미치는 영향에 대해 반대 의견이 존재한다. 따라서 본 총설을 통해 대사 조직에서의 27-하이드록시콜레스테롤 역할에 대한 논의와 함께, 죽상 동맥 경화증 및 대사 증후군에 영향을 주는 27-하이드록시콜레스테롤의 세부 기전에 대해 논의하고자 한다.