• Asian Pacific Journal of Cancer Prevention
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• 제13권3호
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• pp.979-983
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• 2012

Background : Previous studies have suggested a lack of complete cross-resistance between steroidal (exemestane) and non-steroidal aromatase inhibitors (nSAI). Methods : Eighty-eight metastatic breast cancer (MBC) patients who received 25 mg of exemestane orally once a day at the National Cancer Center, Korea, between 2003 and 2009, were reviewed retrospectively. All patients had received nSAI for metastatic disease prior to exemestane therapy. Results : The median age was 52 years (range, 33-79), and 13 (14.8%) patients were premenopausal who concomitantly received GnRH agonist. Exemestane was given as a second- (80.7%) or third-line (19.3%) hormone therapy. The clinical benefit (CB) rate (complete response + partial response + stable disease ${\geq}$ 24 weeks) was 30.7%, with a median CB duration of 10.0 months (range, 6.3-78.7). The median progression-free survival (PFS) was 3.0 months (95% confidence interval [CI], 1.99-4.01) and the overall survival (OS) 21.5 months (95% CI, 17.96-25.04), with a median followup of 50.3 months. Patients who achieved CB had longer OS than those patients who did not (29.6 vs 17.9 months; P=0.002). On univariate analysis of predictive factors, patients who had achieved CB from previous nSAI tended to show lower CB rate (24.6% vs 44.4%, respectively; P=0.063) and shorter PFS (2.8 vs 4.8 months, respectively; p=0.233) than patients who had not. Achieving CB from previous nSAI became independent predictive factor for CBR to exemestane on multivariable analysis (Odds ratio = 2.852, P = 0.040). Conclusions : Exemestane after nSAI failure was effective in prolonging CB duration. The drug's efficacy seemed to be inferior in patients who had benefit from previous nSAI use.

• Animal cells and systems
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• 제13권4호
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• pp.439-445
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• 2009

Cytochrome P450 aromatase (P450arom) catalyzes the conversion of androgens to estrogens and plays an important role in reproduction and development in vertebrates. We investigated the expression patterns of ovarian P450arom (P450aromA) and brain P450arom (P450aromB) mRNA during sex change in black porgy. Maturity was divided into seven stages from male to female (immature testis, mature testis, testicular portion of mostly testis, ovarian portion of mostly testis, testicular portion of mostly ovary, ovarian portion of mostly ovary, and mature ovary). P450aromA expression was significantly higher in the ovarian portion of mostly-ovarian stage fish, and P450aromB expression was highest in the brain of black porgy with mostly-ovarian gonads. Histology showed that testicular tissues were disintegrated with the development of ovarian tissue associated with an increase in the expression of the two P450arom mRNAs during sex change. Interestingly, among various tissues, P450aromA was only expressed in the ovary, and P450aromB was only expressed in the brain. To understand the role of gonadotropin-releasing hormone (GnRH) and estradiol ($E_2$), we injected exogenous hormone (GnRH analogue [GnRHa] and $E_2$) into immature black porgy. In the GnRHa group, expression of the two P450arom genes decreased 12 h after injection, and expression of the two P450arom genes were significantly higher at 6 dafter $E_2$ injection. These results provide useful baseline knowledge on the mechanism of natural sex change in black porgy.

• 여성건강간호학회지
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• 제27권1호
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• pp.49-57
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• 2021

Purpose: Aromatase inhibitors (AIs) are widely prescribed for postmenopausal women with breast cancer and are known to cause musculoskeletal pain. This study aimed to identify factors associated with AI continuation intention among breast cancer survivors (BCS). Methods: A cross-sectional survey was conducted on 123 BCS (stages I-III), who had been taking AIs for at least 6 weeks. Participants were recruited from a cancer center in Goyang, Korea, from September to November 2019. Descriptive statistics, Welch analysis of variance, Pearson correlation coefficients, and simple linear regression were used for the analysis. Results: Beliefs about endocrine therapy was a significant predictor of AI continuation intention (β=.66, p<.001). The majority of participants (87.0%) reported experiencing musculoskeletal pain since taking AIs and the score for the worst pain severity within 24 hours was 5.08±2.80 out of 10. Musculoskeletal pain, however, was not associated with AI continuation intention. Fear of cancer recurrence (FCR) was clinically significant (≥13) for 74.0% of the respondents (mean, 17.62±7.14). Musculoskeletal pain severity and pain interference were significantly associated with FCR (r=.21, p<.05; r=.35, p<.01, respectively). Pain interference was significantly associated with beliefs about endocrine therapy (r=-.18, p<.05). Conclusion: AI continuation intention can be modified by reinforcing patients' beliefs about endocrine therapy. Musculoskeletal pain may have a negative effect on beliefs about endocrine therapy and increase FCR among BCS. Thus, awareness of musculoskeletal pain during AI therapy should be raised and further research is required to develop multidisciplinary pain management strategies and clinical guidelines to reinforce beliefs about endocrine therapy.

• Animal Bioscience
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• 제35권11호
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• pp.1666-1674
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• 2022

Objective: Letrozole, a potent aromatase inhibitor, is known to have the potential to modify male reproductive function by altering sex hormone levels. This study aimed to evaluate the semen and testicular characteristics and hormonal profile of aged Mrakhoz bucks (Capra hircus) treated with letrozole. Methods: Twelve Markhoz male goats, aged between 4.5 to 5.5 years with an average body weight (BW) of 61.05±4.97 kg were used for the study. Animals were randomly divided into two equal groups and subcutaneously received either 0.25 mg/kg BW of letrozole or a control every week for 2 months. The semen collections were performed every 10 days, and blood samples and testicular biometric records were collected at 20 days intervals. Results: Letrozole causes increased testosterone and follicle-stimulating hormone levels, testosterone to estradiol ratio, semen index and reaction time during the period from 20th to 60th days (p<0.05). Furthermore, letrozole-treated bucks had higher semen volume, sperm concentration, and total sperm per ejaculate from 30th to 60th days (p<0.05). However, no differences occurred between the groups in scrotal circumference, relative testicular volume, semen pH, abnormality, acrosome integrity, and membrane integrity of sperm during the study (p>0.05). The serum luteinizing hormone levels, sperm viability, motility, and progressive motility increased, and estradiol levels decreased after 40th to 60th days of letrozole treatment (p<0.05). Conclusion: Letrozole application to aged Markhoz bucks provokes reproductive hormonal axis which, in turn, induces enhancement of semen production and quality.

• Genomics & Informatics
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• 제21권2호
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• pp.20.1-20.10
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• 2023

Aromatase inhibitors (AI) are drugs that are widely used in treating estrogen receptor (ER)-positive breast cancer patients. Drug resistance is a major obstacle to aromatase inhibition therapy. There are diverse reasons behind acquired AI resistance. This study aims at identifying the plausible cause of acquired AI resistance in patients administered with non-steroidal AIs (anastrozole and letrozole). We used genomic, transcriptomic, epigenetic, and mutation data of breast invasive carcinoma from The Cancer Genomic Atlas database. The data was then separated into sensitive and resistant sets based on patients' responsiveness to the non-steroidal AIs. A sensitive set of 150 patients and a resistant set of 172 patients were included for the study. These data were collectively analyzed to probe into the factors that might be responsible for AI resistance. We identified 17 differentially regulated genes (DEGs) among the two groups. Then, methylation, mutation, miRNA, copy number variation, and pathway analyses were performed for these DEGs. The top mutated genes (FGFR3, CDKN2A, RNF208, MAPK4, MAPK15, HSD3B1, CRYBB2, CDC20B, TP53TG5, and MAPK8IP3) were predicted. We also identified a key miRNA - hsa-mir-1264 regulating the expression of CDC20B. Pathway analysis revealed HSD3B1 to be involved in estrogen biosynthesis. This study reveals the involvement of key genes that might be associated with the development of AI resistance in ER-positive breast cancers and hence may act as a potential prognostic and diagnostic biomarker for these patients.

• Journal of Animal Science and Technology
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• 제50권6호
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• pp.783-792
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• 2008

본 연구는 생후 발달과정에서 숫 흰쥐의 생식기인 Efferent ductules(EDs)과 부정소에서 cytochrome P450 aromatase(Cyp19) 유전자의 발현과 연령별 발현 양상을 알아보는데 목적이 있다. 조직으로부터 추출된 total RNA는 역 전사 반응을 통해 cDNA로 바뀌어진 후 real-time PCR 기법을 사용하여 부위별 그리고 연령별로 Cyp19 유전자 발현을 알아보았다. Cyp19 유전자의 발현은 EDs에서 90일령을 제외한 7일, 14일, 그리고 30일령 등 성숙기 이전의 모든 연령에서 나타났으며, 부정소에서는 7일령을 제외한 모든 연령에서 보여졌다. 특히 부정소에서 Cyp19의 발현은 부정소의 각 부위별로 특이한 양상을 보였다. 본 연구 결과를 통해 남성 생식기의 EDs와 부정소의 각 부분에서 Cyp19 유전자 발현은 연령과 부위에 따라 차별적으로 조절되는 것을 알 수 있었다.

• 대한생식의학회:학술대회논문집
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• 대한불임학회 2004년도 제47차 추계학술대회
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• pp.85.2-86
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• 2004

• 한국수정란이식학회지
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• 제25권4호
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• pp.273-279
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• 2010

Follicular cystic follicles (FCFs) show delayed regression with persistent follicle growth. However, the mechanism by which follicles are persistently grown remains unclear. Glutathione S-transferases (GSTs) are drug-metabolizing and detoxification enzymes that are involved in the intracellular transport and metabolism of steroid hormones. In this study, a proteomic analysis was performed to identify whether GST expression is changed in bovine FCFs and to predict the interactions between GST and other proteins. Normal follicles and FCFs were classified based on their sizes (5 to 10 mm and 25 mm). In bovine follicles, GST mu 1 (GSTM1) was detected as a differentially expressed protein (DEP) and significantly up-regulated in FCFs compared to normal follicles (p<0.05). Consistent with the proteomic results, semi-quantitative PCR data and western blot analysis revealed an up-regulation of GSTM1 in FCFs. Expression levels of aromatase and dehydrogenase proteins were changed in FCFs. These results show that the up-regulation of GSTM1 that is observed in bovine FCFs is likely to be responsible for the persistent follicle growth in FCFs as the activity of aromatase and the dehydrogenases.

• Archives of Pharmacal Research
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• 제28권12호
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• pp.1365-1375
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• 2005

The antiestrogenic effects of marijuana smoke condensate (MSC) and three major cannabinoids, i.e., $\bigtriangleup^{9}$-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN), were evaluated using in vitro bioassays, viz., the human breast cancer cell proliferation assay, the recombinant human estrogen receptor (ER) competitive binding assay, and the reporter gene assay. The inhibitory effects on estrogen were also examined using the ethoxyresorufin-O­deethylase (EROD) assay, the aromatase assay, and the 17$\beta$-estradiol ($E_{2}$) metabolism assay. The results showed that MSC induced the antiestrogenic effect via the ER-mediated pathway, while THC, CBD, and CBN did not have any antiestrogenic activity. This suggests that the combined effects of the marijuana smoke components are responsible for the antiestrogenicity of marijuana use. In addition, MSC induced the CYP1A activity and the $E_{2}$ metabolism, but inhibited the aromatase activity, suggesting that the antiestrogenic activity of MSC is also related to the indirect ER-dependent pathway, as a result of the depletion of the in situ $E_{2}$ level available to bind to the ER. In conclusion, pyrogenic products including polycyclic aromatic hydrocarbons (PAHs) in the non-polar fraction, which is the most biologically active fraction among the seven fractions of MSC, might be responsible for the antiestrogenic effect.

• 한국발생생물학회지:발생과생식
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• 제11권3호
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• pp.187-193
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• 2007

Ethane 1,2-dimethane sulfonate(EDS)는 Leydig 세포의 선별적 사멸을 유도하는 약물로서 가역적인 테스토스테론 결핍 흰쥐를 만드는데 널리 사용된다. 부정소의 구조와 기능 유지는 크게 보아 정소에서 분비되는 테스토스테론에 의존적이지만, 테스토스테론으로부터 유도되는 dihydroxytestosterone(DHT)와 에스트로겐도 중요한 역할을 한다. 본 연구에서는 EDS 주사 후 7주까지 부정소에서의 스테로이드 호르몬 수용체, cyctochrome P450aromatase(P450arom)와 $5{\alpha}$-reductase의 유전자 발현 양상을 조사하였다. 성숙한 수컷 흰쥐($350{\sim}400\;g$)에 EDS를 1회 복강 주사하고(75 mg/kg i.p.) 주사 후 0, 1, 2, 3, 4, 5, 6, 7주가 경과한 날에 희생하였다. 표적 유전자들의 전사 활성은 반 정량적 역전사 중합효소 반응법(semi-quantitative RT-PCRs)으로 측정하였다. Estrogen receptor alpha($ER{\alpha}$) 전사 수준은 EDS 실험군에서 대조군에 비해 주사 1주후에 유의하게 상승했으나(P<0.01) 2주 후부터는 대조군과 유의적인 차이를 보이지 않았다. Estrogen receptor beta($ER{\beta}$)의 전사 수준은 주사 1주후 EDS 실험군에서 대조군에 비해 유의하게 증가했다가(P<0.05), 2주와 3주에는 감소하였고(P<0.05와 P<0.01), 4주와 6주까지는 변동폭을 보이다가 7주 후에는 대조군에 비해 증가하였다(P<0.05). Androgen receptor(AR) 전사 수준은 주사 2주 후에 유의하게 증가하다가(P<0.01) 3주 후부터는 대조군 수준으로 회복하였다. 반면, P450arom는 주사 1주 후부터 3주까지 급격하게 감소했다가(P<0.01 1주와 2주; P<0.05 3주), 4주에 대조군 수준으로 회복하였다. $5{\alpha}$-reductase type 2($5{\alpha}$-RT2)의 mRNA 수준은 4주 후 유의하게 증가했다가(P<0.01), 이후 대조군 수준으로 회복하였다. 본 연구는 EDS 주사가 성 스테로이드 호르몬 수용체들과 안드로겐 전환 효소들의 전사 활성에 가역적인 변화를 유도함을 보여준 것이다. EDS 주사 모델은 부정소의 생리 조절 기작을 이해하는데 유용할 것으로 사료된다.