• 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-${\beta}$.

• 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.

• Korean Journal of Clinical Pharmacy
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• v.30 no.1
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• pp.1-10
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• 2020

Objective: The aim of the study was to perform a meta-analysis of randomized clinical trials to compare the clinical efficacy and safety between combination of cyclin-dependent kinase (CDK) 4/6 inhibitors with aromatase inhibitors (AIs) and AIs alone in patients with hormone receptor+/human epidermal growth factor receptor type2-(HR+/HER2-) advanced breast cancer. Methods: Published clinical studies were identified through electronic database searches until February 2019. Literature qualities were assessed by the Scottish Intercollegiate Guidelines Network Checklist. Key endpoints of efficacy were progression-free survival (PFS), objective response rate (ORR), and clinical benefit (CB). Endpoints of safety were adverse events (AEs) (neutropenia, leukopenia, any grade 3/4 AEs, and serious AEs) and on-treatment death. Meta-analysis was performed using the RevMan 5.3 software. Results: The selected five studies were evaluated as "good" in quality assessment. Compared to AIs alone, the combination therapy significantly improved PFS (pooled hazard ratio=0.55; 95% confidence interval (CI) 0.49-0.62), ORR (odds ratio=1.78; 95% CI=1.49-2.13), and CB (odds ratio=1.86; 95% CI=1.51-2.28). The prevalence of AEs was significantly higher in the combination group than in the AIs alone group. On-treatment death was greater in the combination group than in the AIs alone group, although insignificant. Conclusion: The combination therapy of CDK4/6 inhibitors with AIs was more effective for the treatment of HR+/HER2- advanced breast cancer, but less safe than AIs alone. The combination therapy should be effectively managed through patient monitoring, and further studies are needed to reduce AEs in the combination therapy of CDK4/6 inhibitors with AIs.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2819-2822
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• 2013

In this study, antiproliferative effects of the selective estrogen receptor modulator Tamoxifen and the aromatase inhibitor letrozole (Femara) were evaluated and compared using the FM3A cell line, originating from a C3H mouse mammary carcinoma and positive in terms of estrogen receptor (ER) expression. Cell kinetic parameters including labelling index, mitotic index and labelling index were assessed after exposure of the. FM3A cell line to $0.001{\mu}g/ml$ of Tamoxifen and $0.25{\mu}g/ml$ of Femara for 4, 8, 16 and 32 h for all parameters. The results showed that cell growth was inhibited by both agents. There was a significant decrease in labelling index and mitotic index and significant increase in apoptotic index for all experimental groups. The differences between control and all experimental groups were statistically significant (p<0.001) for all applications.

• 대한생식의학회:학술대회논문집
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• 2006.11a
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• pp.158-159
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• 2006

• 대한생식의학회:학술대회논문집
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• 2006.06a
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• pp.159.1-159.1
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• 2006

• 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.

• 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.

• Clinical and Experimental Reproductive Medicine
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• v.35 no.2
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• pp.143-153
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• 2008

Objective: To investigate the effects of aromatase inhibitor on reproductive hormone profiles and evaluate it's ovulation inducing capability in anovulatory infertile women. Methods: We quantified the blood levels of reproductive hormones from 30 healthy normal cycling women in natural cycle (control) and letrozole medicated cycle (study). LH, FSH, estradiol, testosterone, DHEA-S were quantified on third, 11th, 21th day in both cycles, and on 21th day, progesterone was added. Sixth anovulatory infertile women received either letrozole or clomiphene citrate for ovulation induction (n=30 in each groups). We compared the clinical parameters such as ovulation rate, pregnancy rate, the day of LH surge, number of follicles and endometrial thickness, cervical mucus amount, spinnbarkeit, mean diameter of follicles on the day of LH surge. Results: Letrozole had no effect on the LH, FSH, estradiol, DHEA-S secretion but there were significant increase in testosterone level on day 11 and progesterone level on day 21 in letrozole medicated cycle compared than control cycle ($0.40{\pm}0.16$ vs $0.28{\pm}0.11\;ng/ml$, p=0.002, $18.18{\pm}13.07$ vs $8.38{\pm}7.64\;ng/ml$, p=0.001, respectively). In comparison between letrozole and clomiphene groups, there were no significant difference in ovulation rate, pregnancy rate, number of mature follicle, mean diameter of follicles, but showed earlier LH surge, thicker endometrium, more cervical mucus, and higher spinnbarkeit in letrozole group ($12.12{\pm}2.46$ vs $14.52{\pm}3.18$ days, p=0.006, $10.48{\pm}1.23$ vs $8.52{\pm}0.93\;mm$, p=0.000, $2.04{\pm}0.61$ vs $1.57{\pm}0.59$, p=0.012, $6.00{\pm}1.12$ vs $4.95{\pm}1.61\;cm$, p=0.003, respectively). Conclusion: Letrozole may augment folliculogenesis and improve the endometrial condition for implantation in normal cycling women. Ovulation efficacy of letrozole in anovulatory women was comparable to clomiphene citrate and letrozole may be more physiological in ovulation induction.

• Clinical and Experimental Reproductive Medicine
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• v.34 no.4
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• pp.275-283
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• 2007

Objective: This study was performed to investigate the expressions of endometriosis related genes in shed endometrial tissues from menstrual blood of patients with or without endometriosis. Methods: The shed endometrial tissues were collected on 2$^{nd}$ or 3$^{rd}$ day of menstrual cycle with Wallace catheter in patients with endometriosis (n=16) and without endometriosis (n=26). The mRNA expressions of twelve kinds of endometriosis related genes were compared between two groups using semi-quantitative RT-PCR. Results: The collected shed endometrium was confirmed by histological observation. Expressions of telomerase, c-kit and aromatase mRNA were not detected by RT-PCR in shed endometrial tissues. The mRNA expressions of apoptosis related genes (fas, fas ligand, bcl-2, bax), stem cell factor, estrogen receptor-$\alpha$/$\alpha$, endometriosis protein-I and secretory leukocyte protease inhibitor gene were similar between shed endometrial tissues with endometriosis and without endometriosis. Conclusion: We could not find the difference of mRNA expressions of tested endometriosis related genes between shed endometrial tissues with or without endometriosis by semi-quantitative RT-PCR analysis. It may be related to the dynamical changes of gene expressions in the endometrium with menstrual cycle.