• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6359-6364
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• 2015

Background: Preclinical studies have shown that the combination of an aromatase inhibitor (AI) and capecitabine in estrogen receptor (ER)- positive cell lines enhance antitumor efficacy. This retrospective analysis of a group of patients with metastatic breast cancer (MBC) evaluated the efficacy and safety of combined AI with capecitabine. Materials and Methods: Patients with hormone receptor-positive metastatic breast cancer treated between 1st January 2005 and 31st December 2010 with a combination of capecitabine and AI were evaluated and outcomes were compared with those of women treated with capecitabine in conventional dose or AI as a monotherapy. Results: Of 72 patients evaluated, 31 received the combination treatment, 22 AI and 19 capecitabine. The combination was used in 20 patients as first-line and 11 as second-line treatment. Mean age was 46.2 years with a range of 28-72 years. At the time of progression, 97% had a performance status of <2 and 55% had visceral disease. No significant difference was observed between the three groups according to clinical and pathological features. Mean follow up was 38 months with a range of 16-66 months. The median PFS of first-line treatment was significantly better for the combination (PFS 21 months vs 8.0 months for capecitabine and 15.0 months for AI). For second-line treatment, the PFS was longer in the combination compared with capecitabine and Al groups (18 months vs. 5.0 months vs. 11.0 months, respectively). Median 2 year and 5 year survival did not show any significant differences among combination and monotherapy groups. The most common adverse events for the combination group were grade 1 and 2 hand-for syndrome (69%), grade 1 fatigue (64%) and grade 1 diarrhoea (29%). Three grade 3 hand-foot syndrome events were reported. Conclusions: Combination treatment with capecitabine and AI used as a first line or second line treatment was safe with much lowered toxicity. Prospective randomized clinical trials should evaluate the use of combination therapy in advanced breast cancer to confirm these findings.

• Animal cells and systems
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• v.16 no.2
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• pp.127-134
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• 2012

We investigated the effects of fadrozol, an aromatase inhibitor (AI), and $17{\alpha}$-methyltestosterone (MT) on the induction of sex change in juvenile longtooth grouper $Epinephelus$ $bruneus$, via histological observation of gonads. Changes in the mRNA expression of GtH subunits (FSH-${\beta}$ and LH-${\beta}$) in the pituitary, and estradiol-$17{\beta}$ (E2) and 11-ketotestosterone (11-KT) levels in the blood were also surveyed after AI and MT treatment. Juvenile longtooth groupers ($113{\pm}17g\;body\;weight$; $16.2{\pm}1.2cm\;body\;length$) received intramuscular injections of AI at 3 (3-AI) and 5 (5-AI) mg/kg BWdoses and MT at a 5 mg/kg BW (5-MT) dose. At week 7 post-injection, 3-AI and 5-MT oocytes were degenerated, and gonads of the 5-AI group initiated spermatogenesis. At week 21 post-injection, 3-AI- and 5-MT-treated gonads contained spermatogonia and spermatocytes, while 5-AI treatment induced advanced stages of spermatogenesis. The serum E2 level showed no significant differences throughout the experimental period, whereas that of 11-KT was significantly elevated in the 5-AI group at weeks 7 and 21 post-injection. A significant increase in the expression of FSH-${\beta}$ mRNA was evident in the 5-AI group at week 21 post-injection. In contrast, LH-${\beta}$ mRNA expression did not significantly differ among groups during the experimental period. These results imply that sex change has two stages in the longtooth grouper. In the first stage, oocytes are degenerated by the stimulation by 11-KT, and in the second stage spermatogenesis occurs, owing to the co-effects of 11-KT and FSH-${\beta}$.

• Proceedings of the Korean Society of Life Science Conference
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• 2005.09a
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• pp.41-41
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• 2005

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.282.2-283
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• 2002

In situ and circulating estrogen is the most important endocrine hormone that promotes the growth of hormone-dependent breast cancer. Consequently. decrease of estrogen on in situ and circulation can inhibit breast cancer. Estrogen is mainly produced by the ovary in premenopausal women and by peripheral tissues such as adipose tissues in postmenopausal women. The cytochrome p450 (CYP19), aromatase. is a key enzyme in the synthesis of estrogen hormones. (omitted)

• Proceedings of the Zoological Society Korea Conference
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• 2003.08a
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• pp.197.3-197
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• 2003

No Abstract, See Full Text

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2003.10a
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• pp.67-67
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• 2003

Tributyltin chloride (TBTCI) is an organotin compounds that have been widely used as antifouling agents and bioaccumulated in the food chain. TBTCI has been known to induce imposex in female gastropods. There are several reports that TBTCI increased testosterone level and inhibited the conversion of testosterone to estradiol by the aromatase cytochrome P450 enzyme. In this studies, we investigated the effects of TBTCI on steroidogenesis in testes, We dosed to 4-week-old Spragus-Dawleys (SD) male rats with TSTCI (0, 1, 5, 10, and 20mg/kg/day) daily by gavage for 14 days. TBTCI significantly decreased the weights of seminal vesicle, prostate, cowper's gland and LABC at 10 and 20mg/kg/day but significantly Increased the weights of liver at 10 and 20mg/kg/day and adrenals at 20mg/kg/day. mRNA levels of steroidogenic acute regulatory (StAR) and P450 aromatase were decreased and mRNA levels of cytochrome P450 17$\alpha$-hydroxylase/$C_{17-20}$ lyase (P450c17) were increased by TBTCI. TBTCI significantly increased serum testosterone level in dose-dependent manner. From above results, we found that TBTCI altered mRNA levels of enzymes related steroidogenesis, weights of organs and serum testosterone levels. This suggests that change of hormone levels may be due to alteration of mRNA levels of steroidogenic enzyme in testes, but further studies are necessary to investigate hormone levels in testis organ in order to find a relation of enzyme related to steroidogenesis with hormone levels. This work was supported by the Korea FDA Grant KFDA-03131-EDS-010.

• Archives of Plastic Surgery
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• v.45 no.5
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• pp.432-440
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• 2018

Background Adjuvant therapy after breast surgery, including tamoxifen or aromatase inhibitors, improves the postoperative outcomes and long-term survival of breast cancer patients. The aim of this study was to determine whether volume changes occurred in the contralateral breast during hormonal or other adjuvant therapies. Methods This study reviewed 90 patients who underwent unilateral breast reconstruction between September 2012 and April 2018 using tissue expanders and a permanent implant after the surgical removal of breast cancer. The volume of the contralateral breast was measured using a cast before the first (tissue expander insertion) and second (permanent implant change) stages of surgery. Changes in breast volume were evaluated to determine whether adjuvant therapy such as hormonal therapy, chemotherapy, and radiation therapy influenced the volume of the contralateral breast. Results The group receiving tamoxifen therapy demonstrated a significant decrease in volume compared with the group without tamoxifen (-7.8% vs. 1.0%; P=0.028). The aromatase inhibitor-treated group showed a significant increase in volume compared with those who did not receive therapy (-6.2% vs. 4.5%; P=0.023). There were no significant differences between groups treated with other hormonal therapy, chemotherapy, or radiation therapy. Conclusions Patients who received tamoxifen therapy showed a significant decrease in volume in the contralateral breast, while no significant change in weight or body mass index was found. Our findings suggest that we should choose smaller implants for premenopausal patients, who have a high likelihood of receiving tamoxifen therapy.

• Fisheries and Aquatic Sciences
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• v.18 no.2
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• pp.211-220
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• 2015

We investigated the differences in the expression of the neurohormones kisspeptin (Kiss) and gonadotropin-inhibitory hormone (GnIH) and cytochrome P450 aromatase (P450arom), gonadotropin hormones (GTHs), and sex steroids in the goldfish Carassius auratus exposed to light-emitting diodes (LEDs). The expression levels of Kiss1, Kiss2, G-protein-coupled receptor 54 (GPR54), GTHs, GnIH, and P450arom were compared between the control (white light) and LED-treated goldfish. Furthermore, we measured the plasma levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The levels of Kiss1 mRNA and protein; Kiss2, GPR54, and $GTH{\alpha}$ protein; GTH mRNA; and plasma FSH and LH in the hypothalamus and cultured hypothalamus cells were significantly higher in the green and purple LED treatment groups than in the other groups. These results suggested that red LEDs inhibit the sex maturation hormones, Kiss, GPR54, GTHs, and P450arom, and that GnIH plays a role in the negative regulation of reproductive function in goldfish.

• Animal cells and systems
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• v.10 no.4
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• pp.203-209
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• 2006

Azoles are widely used antifungal agents, which inhibit the biosynthesis of fungal cell-membrane ergosterol. In this study, using an amphibian follicle culture system, the effects of azoles on follicular steroidogenesis in frogs were examined. Itraconazole (ICZ), clotrimazole (CTZ) and ketoconazole (KCZ) suppressed pregnenolone ($P_5$) production by the follicles ($ED_{50};\;0.04_{\mu}M,\;0.33_{\mu} M,\;and\;0.91_{\mu}M$, respectively) in response to frog pituitary homogenates (FPH). However, fluconazole (FCZ), miconazole (MCZ) and econazole (ECZ) were not effective in the suppression of $P_5$ production. Not all the azoles examined suppressed the conversion of exogenous $P_5$ to progesterone ($P_4$) (by $3{\beta}$- HSD) or $P_4$ to $17{\alpha}$-hydroxyprogesterone ($17{\alpha}$-OHP) (by $17{\alpha}$-hydroxylase), or androstenedione (AD) to testosterone (T) (by $17{\beta}$-HSD). In contrast, CTZ, MCZ and ECZ in medium partially suppressed the conversion of $17{\alpha}$-OHP to AD (by C17-20 lyase) ($ED_{50};\;0.25{\mu} M,\;4.5{\mu}M,\;and\;0.7{mu}M$, respectively) and CTZ, KCZ, ECZ and MCZ strongly suppressed the conversion of exogenous T to estradiol ($E_2$) (by aromatase) ($ED_{50};\;0.02{\mu}M,\;8{\mu}M,\;0.07{\mu}M,\;0.8{\mu}M$, respectively). These results demonstrated that some azole agents strongly suppress amphibian follicular steroidogenesis and particularly, P450scc and aromatase are more sensitive to azoles than other steroidogenic enzymes.

• Clinical and Experimental Reproductive Medicine
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• v.32 no.1
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• pp.27-32
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• 2005

Objective: To evaluate the effectiveness of aromatase inhibitor (AI) for ovulation induction in polycystic ovary syndrome (PCOS) patients with thin endometrium, hyper-responsiveness after clomiphene citrate (CC) treatment. Material and Methods: A prospective study was performed in 43 PCOS patients (50 cycles) with ovulatory dysfunction between March 2004 and September 2004. AI group (total 36 cycles) included the patients 1) with thin endometrium below 6 mm on hCG day after CC (n=17), 2) with more than 5 ovulatory follicles after 50mg of CC (n=4), 3) who do not want multiple pregnancy (n=14). Patients were treated with Letrozole 2.5mg for days 3 to 7 of the menstrual cycle. CC group (total 14 cycles) were treated with CC 50~100 mg. Results: In PCOS patients, ovulation was occurred 97.2% after AI use. Between AI group and CC group, there was no significant difference in the mean age, duration of infertility, interval of menstruation, basal FSH, prior treatment cycles, and the day of hCG administration. But, the number of mature follicles (${\geq}15mm$) was lower in the AI group ($1.08{\pm}0.45$ vs. $1.64{\pm}0.75$) (p=0.018), and the thickness of endometrium (mm) was significantly thicker in the AI group ($10.35{\pm}1.74$ vs. $9.23{\pm}1.61$) (p=0.044), and E2 (pg/ml) concentration on hCG day was lower in the AI group ($116.9{\pm}75.8$ vs. $479.5{\pm}300.8$) (p=0.001). Among the AI group, patients with prior thin endometrium (below 6 mm) during CC treatment showed $10.6{\pm}1.6mm$ in the endometrial thickness and $106.6{\pm}66.8pg/ml$ in $E_2$ concentration. Patients with more than 5 ovulatory follicles after CC showed decreased follicle number ($1.25{\pm}0.5$) compared to prior CC cycle. Conclusions: In PCOS patients, AI group showed significantly thicker endometrium, lesser number of mature follicles, and lower E2 concentration on hCG day than CC group. AI might be useful alternative treatment for ovulation induction in PCOS patients with thin endometrium and hyper-responsiveness after CC treatment.