• The Korean Journal of Physiology
• /
• v.20 no.2
• /
• pp.271-278
• /
• 1986

These studies were carried out to investigate the effects of the antiestrogens, LY-117018 and tamoxifen, on implantation in ovariectomized or intact adult rats. A Quantity of $80\;{\mu}g$ of LY-l17018 or tamoxifen was given to adult female rats on Day 1, 2, 3 and 4 of pregnancy and investigated the implantation sites on Bay 8 of pregnancy. The rats were ovariectomized at the first day of pregnancy and treated with various doses of LY-l17018 or tamoxifen together with progesterone daily from Day 2 to 8 of pregnancy and then investigated the implantation sites on Day 8 of pregnancy The results were summarized as follows; When a single dose of $80\;{\mu}g$ LY-l17018 and tamoxifen was given during the first 4 days of pregnancy, the implantation was intesively inhibited in the pregnant rat treated with LY-l17018 on Day 2 $(14.4{\pm}3.5%),\;3(16.3{\pm}5.3%)\;and\;tamoxifen\;on\;Days\;2\;(17.4{\pm}4.6%),\;3\;(16.3{\pm}2.8%)\;and\;4\;(13.9{\pm}3.5%).$ LY-l17018 was apt to inhibit more potently the implantation than tamoxifen except on Day 4 of pregnancy In rats ovariectomized on Day 1 of pregnancy and treated continucusly with 12? r9 of LY-117018 and tamoxifen together with progesterone showed the highest implantation rate, compared with the rats treated continuously with different doses of the two drugs. The correlation coefficients between the dosage of drugs and implantation rate were r= 0.91 (LY-117018), 0.51 (tamoxifen), respectively, except treatment with $625\;{\mu}g$ of the drugs. Tamoxifen was apt to stimulate the implantation more potently than LY-l17018 except groups treated with $625\;{\mu}g$ of the two drugs.

• The Korean Journal of Physiology and Pharmacology
• /
• v.6 no.4
• /
• pp.187-191
• /
• 2002

Tamoxifen, an antiestrogen, has previously been shown to induce apoptosis in HepG2 human hepatoblastoma cells through activation of the pathways independent of estrogen receptors, i.e., intracellular $Ca^{2+}$ increase and generation of reactive oxygen species (ROS). However, the mechanism of tamoxifen to link increased intracellular $Ca^{2+}$ to ROS generation is currently unknown. Thus, in this study we investigated the possible involvement of calmodulin, a $Ca^{2+}$ activated protein, and $Ca^{2+}$/calmodulin-dependent protein kinase II in the above tamoxifen-induced events. Treatment with calmodulin antagonists (calmidazolium and trifluoroperazine) or specific inhibitors of $Ca^{2+}$/calmodulin-dependent protein kinase II (KN-93 and KN-62) inhibited the tamoxifen-induced apoptosis in a dose-dependent manner. In addition, these agents blocked the tamoxifen-induced ROS generation in a concentration-dependent fashion, which was completely suppressed by intracellular $Ca^{2+}$ chelation. These results demonstrate for the first time that, despite of its well-known direct calmodulin-inhibitory activity, tamoxifen may generate ROS and induce apoptosis through indirect activation of calmodulin and $Ca^{2+}$/calmodulin-dependent protein kinase II in HepG2 cells.

• Radiation Oncology Journal
• /
• v.32 no.4
• /
• pp.262-265
• /
• 2014

Tamoxifen and radiotherapy are used in breast cancer treatment worldwide. Radiation recall dermatitis (RRD), induced by tamoxifen, has been rarely reported. Herein, we report a RRD case induced by tamoxifen. A 47-year-old woman had a right quadrantectomy and an axillary lymph node dissection due to breast cancer. The tumor was staged pT2N0; it was hormone receptor positive, and human epidermal growth factor receptor 2 negative. The patient received adjuvant chemotherapy followed by tamoxifen and radiotherapy. After 22 months of tamoxifen, the patient developed a localized heating sensation, tenderness, edema, and redness at the irradiated area of the right breast. The symptoms improved within 1 week without treatment. Three weeks later, however, the patient developed similar symptoms in the same area of the breast. She continued tamoxifen before and during dermatitis, and symptoms resolved within 1 week.

• Clinical and Experimental Reproductive Medicine
• /
• v.15 no.2
• /
• pp.93-102
• /
• 1988

These studies were undertaken to examine the relationship between tamoxifen and sex steroid hormones in rat uterine morphology and the effect of tamoxifen on sex steroid hormone levels, implantation and myometrial contraction. The results obtained were as follows : 1) The increase in height of the luminal epithelium caused by tamoxifen treatment was blocked by progesterone. The increase in height of luminal epithelium caused by $estradiol-17{\beta}$ treatment was blocked by tamoxifen. 2) When a single dose of tamoxifen(10, 20, $40{\mu}g$) was given on Day 2 of pregnancy, implantation was prevented. Plasma $estradiol-17{\beta}$ level fell in a dose-dependent manner but plasma progesterone level was constant. 3) In vitro, tamoxifen decreased rat uterine contractility in a dose-dependent manner.

• Archives of Plastic Surgery
• /
• v.44 no.5
• /
• pp.378-383
• /
• 2017

Background This study aimed to assess the effects of the topical application of tamoxifen on wound healing of burned skin in Wistar rats by evaluating 3 healing characteristics: fibrotic tissue thickness (FTT), scar surface area (SSA), and angiogenesis in the healed scar tissue. Methods Eighteen male Wistar rats were used in this study. A third-degree burn wound was made on the shaved animals' back, measuring $2{\times}2{\times}2cm$. In the first group, a 2% tamoxifen ointment was applied to the wound twice daily for 8 weeks. The second group received a placebo ointment during the same period. The third group did not receive any treatment and served as the control group. Results The median (interquartile range=[Q1, Q3]) FTT was 1.35 (1.15, 1.62) mm, 1.00 (0.95, 1.02) mm, and 1.25 (0.8, 1.5) mm in the control, tamoxifen, and placebo groups, respectively (P=0.069). However, the FTT in the tamoxifen group was less than in the placebo and control groups. The median angiogenesis was 3.5 (3.00, 6.25), 8.00 (6.75, 9.25), and 7.00 (5.50, 8.25) vessels per high-power field for the control, tamoxifen, and placebo groups, respectively (P=0.067). However, the median angiogenesis was higher in the tamoxifen group than in the control group. No significant difference was observed in the mean SSA between the tamoxifen group and the control group (P=0.990). Conclusions Local application of tamoxifen increased angiogenesis and decreased the FTT, with no change in the SSA in burned skin areas. These effects are expected to expedite the wound healing process, reducing contracture and preventing hypertrophic scar and keloid formation.

• Analytical Science and Technology
• /
• v.17 no.4
• /
• pp.322-336
• /
• 2004

The improved derivatization technique of tamoxifen metabolite in human urine is described for the acylation method that they are substituted by derivatization reagent like acyl anhydride for use of gas chromatography/mass spectrometry. The hydroxyl group of tamoxifen metabolite was derivatized by trifluoroacetic anhydride (TFAA), pentafluoroacetic anhydride (PFPA) and heptaflorobutylic anhydride (HFBA). It was investigated to the gas chromatography/mass spectrometry (GC/MS) technique use negative ion chemical ionization (NCI), positive ion chemical ionization (PCI) and electron impact (EI). In acylation of the metabolites of tamoxifen, the effective reaction temperature and time were shown to be at $50^{\circ}C$ for 30 min. The 4-hydroxytamoxifen, which is known to major metabolite of tamoxifen, was not detected in human urine, whileas the hydroxymethoxytamoxifen was detected. We thought that this result was from the single dose of tamoxifen.

• The Korean Journal of Pharmacology
• /
• v.26 no.2
• /
• pp.167-176
• /
• 1990

In the present study, we examined the effects of tamoxifen and LY117018 on various parameters for the estrogenic actions in order to understand the mechanism by which tamoxifen and LY117018 act on the uterine cells in 21-23 day old immature rats. Tamoxifen and LY117018 stimulated uterine weight and uterine contents of DNA, protein, and peroxidase activity in the absence of estradiol while inhibited above parameters in the presence of estradiol. Both cytosolic and nuclear progesterone receptors were increased by the treatment of tamoxifen and LY117018 as well as estradiol, but estradiol-induced increase in the progesterone receptors were reduced by the treatment of antiestrogens. These effects were enhanced by the multiple injections of antiestrogens. It seemed that tamoxifen was more agonistic than LY117018 but less antagonistic than LY117018, judged by their effects on various parameters for the estrogenic action. The affinities of estradiol, tamoxifen, and LY117018 for the estrogen receptor were $0.17{\pm}0.01nM(100%)$, $1.10{\pm}0.01nM(6.3%)$, and $0.23{\pm}0.01nM(77%)$, respectively. Furthermore, LY117018 was the competitive ligand for the estrogen receptor in dose-related manner but tamoxifen was not. Following estradiol treatment, nuclear estrogen receptor was sharply increased by 1 h, reaching the maximum by 16 h, while tamoxifen and LY117018 slightly increased nuclear estrogen receptor by 1 h and then decreased thereafter. It is therefore concluded that LY117018 is a competitive antagonist for the estrogen receptor with less estrogenic activity, compared to tamoxifen with low affinity to the estrogen receptor, and tamoxifen may act through other binding site than the estrogen receptor.

• Archives of Pharmacal Research
• /
• v.20 no.6
• /
• pp.572-578
• /
• 1997

To gain further insight into how antiestrogens modulate cell function, the effects of antiestrogen on cell proliferation were studied in human breast cancer cells. We examined the effects of trans-tamoxifen on the proliferation of three human breast cancer cell lines that differed in their estrogen receptor contents. Trans-tamoxifen $(1{\mu}M)$ markedly inhibited the estrogen stimulated proliferation of MCF-7 human breast cancer cells that contained high levels of estrogen receptor $(1.15{\pm}0.03 pmole/mg protein)$ over that of control. In T47D cells that contained low levels of estrogen receptor $(0.23{\pm}0.05 pmole/mg protein)$, trans-tamoxifen $(1{\mu}M)$ showed minimal inhibition of estrogen stimulated cell proliferation over that of control. MDA-MB-231 cells, that contained no detectable levels of estrogen receptors, had their growth unaffected by trans-tamoxifen treatment. These results showed their sensitivity to growth inhibition by antiestrogen conrrelated well with their estrogen receptor content. Also we examined the effect of antiestrogen on cellular progestrone receptor level as well as plasminogen activator activity in MCF-7 cells. Trans-tamoxifen $(1{\mu}M)$ showed maximal inhibition of estrogen stimulated progestrone receptor level as well as plasminogen activator activity in MCF-7 cells that were stimulated by estrogen. It is not clear whether these inhibitions of progestrone receptor and plasminogen activator activity by estrogen are related to the antiestrogen inhibition of cell proliferation of MCF-7 cells. From the results of this study, it is clearly demonstrated that trans-tamoxifen is an antiestrogen in MCF-7 human breast cancer cells. Our data suggest that the biological effectiveness of trans-tamoxifen appear to result from its affinity of interaction with the estrogen receptor.

• Journal of Korean Neurosurgical Society
• /
• v.57 no.3
• /
• pp.204-207
• /
• 2015

We are reporting an unusual case of dural arteriovenous fistula (AVF) of the superior sagittal sinus (SSS) after tamoxifen treatment for breast cancer. A 30-year-old female arrived at the emergency room with a sudden headache and left sided weakness and sensory loss. In her past medical history, she was diagnosed with breast cancer 1 year prior, and subsequently underwent a breast conserving mastectomy with whole breast radiation and adjuvant chemotherapy with tamoxifen. At the time of admission, computed tomography showed a small acute intracerebral hemorrhage at the right parietal cortex, and magnetic resonance imaging showed that a dural AVF at the SSS with a prominent and tortuous venous enhancement along the centrum semiovale was present. Cerebral angiography showed that the dural AVF at the mid-portion of the SSS with meningeal arterial feeding vessels entering the wall of the SSS, then draining through the dilated cortical veins. Our patient had no signs of active malignancy or any abnormalities in her coagulation profile, so it can be concluded that the tamoxifen was the likely cause of the SSS thrombosis and dural AVF. The dural AVF was treated by an endovascular coil embolization for the arterialized segment of the SSS. The patient dramatically recovered favorably from left side motor and sensory deficit. The best clinical approach is to screen potential patients of tamoxifen hormonal therapy and educate them on the sign and symptoms of life threatening thromboembolic events while taking tamoxifen.

• The Journal of Internal Korean Medicine
• /
• v.44 no.1
• /
• pp.53-65
• /
• 2023

Objective: The purpose of this study is to report two cases of breast cancer patients whose side effects after Tamoxifen were treated with traditional Korean medicine. Methods: Two breast cancer patients underwent Tamoxifen after breast-conserving surgery, and both were treated with traditional Korean medicine. Subjective discomfort symptoms were evaluated using the Numerical Rating Scale. Adverse events were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0. Results: After treatment with traditional Korean medicine, the discomfort symptoms that occurred after Tamoxifen, such as osteoarthritis, hot flushes, and cold sweat, all gradually improved. In addition, no hematologic, hepatic, or renal side effects were observed from the traditional Korean medicine treatment. Conclusion: This case study suggests that traditional Korean medicine may contribute to the improvement of side effects caused by Tamoxifen and enhance the quality of life of patients.