• Clinical and Experimental Reproductive Medicine
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• 제33권2호
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• pp.105-113
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• 2006

목 적: 본 연구를 통해 $TGF-{\beta}1$에 의해 유도된 인간자궁내막의 탈락막화 과정에서 ERK와 $PPAR{\gamma}$의 역할을 규명하고자 하였다. 연구방법: 자궁내막 기질세포는 DMEM/F12 (10% FBS, 1 nM E2 and 100 nM P4) 조건에서 배양하였다. 연구 목적에 따라 $TGF-{\beta}1$ (5 ng/ml), Rosiglitazone (50 nM)와 PD98059 ($20{\mu}M$)를 배양액에 첨가하였다. Trypan-Blue와 hematocytometer를 이용하여 현미경하에서 세포의 개수를 측정하였다. Enzyme-linked immunosorbent assay (ELISA)와 western blotting 방법을 사용하여 단백질의 발현 정도를 관찰하였다. 결과 및 결론: 배양액에 $TGF-{\beta}1$을 첨가하여 세포의 증식 정도를 측정한 결과 $TGF-{\beta}1$이 세포의 증식을 억제하는 것을 알 수 있었다. 또한 배양된 세포로부터 PGE2 및 prolactin의 발현을 유도하는 것을 알 수 있었다. 이러한 $TGF-{\beta}1$의 작용은 Smad 및 ERK의 활성화를 통하여 일어남을 알 수 있었다. $PPAR{\gamma}$의 기질인 rosiglitazone을 배양액에 첨가한 결과 $TGF-{\beta}1$에 의한 세포 증식의 억제가 역전되는 것을 알 수 있었다. 뿐만 아니라, 세포 내 ERK의 활성 역시 억제 시켰으며 이 결과 PGE2와 prolactin의 발현이 억제 되는 것을 관찰할 수 있었다. 따라서 본 연구를 통해 $TGF-{\beta}1$에 의한 자궁내막 기질세포의 탈락막화는 Smad와 ERK의 활성화를 통하여 이루어지며 이러한 과정은 $PPAR{\gamma}$에 의해 억제됨을 알 수 있었다.

• 생명과학회지
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• 제33권1호
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• pp.102-113
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• 2023

본 총설에서는 지난 수년 동안 자궁내막 염증 관련 새롭게 밝혀진 에스트로겐과 프로게스테론 수용체의 기능 중 지엽적 에스트로겐의 합성, 특이적 에스트로겐 수용체의 조절, 프로게스테론 저항성 그리고 스테로이드 호르몬의 작용에 의한 자궁내막 조직세포의 염증반응, 분화 및 생존에 대한 세포 및 분자적 조절기전들을 고찰한다. 자궁내막 조직 기질세포의 비정상적인 후성유전체적 변화는 자궁내막증의 발병과 진행에 중요한 요인으로 작용한다. 특히, 에스트로겐 수용체 유전자들의 차별적 메틸화는 기질세포내 ERα로부터 ERβ로의 발현 우세도 전환을 유도하여, ERβ-매개 염증반응, 프로게스테론 저항성 및 레티노이드 합성장애 등의 비정상적인 에스트로겐 반응을 초래한다. 이 기질세포는 또한 PGE2 및 SF-1 매개에 의한 스테로이드 합성효소의 발현유도를 통하여 지엽적 에스트로겐의 생성을 촉진하며, 증가된 에스트라디올은 다시 ERβ에 피드백으로 작용하여 COX-2 촉진을 통한 염증반응의 악순환을 야기한다. 높은 ERβ의 발현은 중간엽 줄기세포의 염색질 구조변화릉 야기하여 프로게스테론 저항성을 획득하고, 이는 반복적 생리에 따른 지속적 노출로 자궁내막 조직의 염증을 형성하며, 이후에는 ERβ-매개 에스트로겐과 TNF-α 및 TGF-β1을 포함한 염증 유발 인자들이 작용하여 염증 조직세포의 부착, 혈관생성 및 생존과 기질세포의 분화조절장애를 유도한다. 따라서, 생리주기의 역동적인 호르몬 변화와 이에 따르는 자궁내막 조직의 핵수용체 신호전달 조절기전에 대한 구체적인 이해는 정상적인 생식기능을 유지하면서 자궁내막증과 같은 비정상적 염증질환을 치료하기 위한 새로운 안목을 제공할 수 있을 것으로 기대된다.

• 대한수의학회지
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• 제34권3호
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• pp.435-439
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• 1994

The present observation was focussed mainly on the histopathological and immunohistochemical finding of the tumor developing from the outside of rat uterus wall. In gross finding, this tumor were a oval form mass and 0.75cm and 1cm in greatest demension. The sectioned surface showed uniform, solid, gray-white. In histopathological finding, the tumor showed the form of lymphoid nodule-like structure and was composed of the cells with karryorrhexis, karyolysis and necrosis in the central zone, mature cells in the paracentral zone, and concentric layers of compressed, flattened and atrophied smooth muscle fibers by the proliferating of the cells closely resembling endometrial stromal ells in the peripheral zone and a few smaller nodule-like structure in certain areas of the peripheral zone. In immunohistochemical observations, the proliferating cells presents only among the concentric layers of the smooth muscle fibers in the peripheral zone. Labeling index of proliferating cells in the peripheral zone was $4.34{\pm}1.28%$. These tumor cells did not metastasized in another orgns and labeling index was low, So it was concluded that this tumor was benign stomal sarcoma.

• Clinical and Experimental Reproductive Medicine
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• 제27권2호
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• pp.117-131
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• 2000

Objectives: To develop a new immunohistochemical marker system for supplementation of the Noyes histological classification of the endometrium in women of child bearing age with regular menstrual cycles, and to employ this system to evaluate pathologic factors involved in endometriosis, and thus to ascertain if it is useful in diagnosis. Materials and Methods: Endometrial biopsies were sampled from the posterior fundus of 41 (24 proliferative phases, 17 secretory phases) women with regular menstrual cycles (28-32 days), and each sample was immunohistochemically stained according to Noyes et al (1975) for determination of expression for estrogen receptor (ER), progesterone receptor (PR), integrin ${\alpha}_1$, ${\alpha}_4$, ${\beta}_3$, COX-1 and COX-2. Then, the PR, integrin ${\beta}_3$ and COX-2 which were clearly expressed in the luteal phase was with endometrial samples were obtained from 20 cases of normal patients (group 1) and 25 cases with endometriosis (group 2) after confirming the day of ovulation by sex steroid level measurements 7-8 days after ovulation Results: In the regular menstruation group the expression of ER showed a tendency to be increased in the proliferative phase and decreased in the secretory phase, and was the highest in the proliferative phase. However, PR in the stromal cells showed no change in the entire menstrual cycle while in the epithelial cells, PR reached a peak in the late proliferative phase and was almost absent in the secretory phase. Integrin (${\alpha}_1$, ${\alpha}_4$, and ${\beta}_3$ expression in the epithelial cells was absent in the proliferative phase but ${\alpha}_1$ was strongly expressed starting from the early secretory phase into the entire secretory phase. ${\alpha}_4$ was expressed strongly in the early and mid secretory phases and disappeared in the late proliferative phase, while ${\beta}_3$ appeared after the mid secretory phase and continued to be expressed until the late secretory phase. Expression in the stromal cells was weak overall and did not show any cyclic pattern. COX-1 expression was shown as a cyclic pattern in the stromal and epithelial cells and was particularly strongly expressed in the mid secretory phase of epithelial cells, and in the mid secretory and menstruation phase of stromal cells. In the endometrial epithelial cells there was strong expression during the entire cycle with stronger expression in the secretory phase compared to the prolferative phase. COX-2 was clearly expressed in the late proliferative, early and mid secretory phases in the stromal cells. No expression was observed in the proliferative phase of the epithelial cells, but which began to appear in the early secretory phase reaching a significant pattern from the mid secretory phase onwards. There was almost no expression in the stromal cells. In the cases with endometriosis showing normal endometrial maturation according to the Noyes classification, PR expression was increased while Integrin-${\beta}_3$의 expression was significantly decreased compared to the normal group. Also, COX-2 expression was slightly decreased in the stromal cells of patients with endometriosis while it was significantly increased in the stromal cells. Conclusion: Immunohistochemical markers can supplement the original Noyes classification of histological endometrial dating and therefore ascertain existing pathologic conditions. Particularly for patients with endometriosis with normally mature endometrial cells, changes in COX-2 and integrin expression patterns may assist in elucidating pathophysiologic mechanisms and therefore aid in the diagnosis of abnormal implantation conditions, and consequently determine a treatment modality.

• Asian Pacific Journal of Cancer Prevention
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• 제16권13호
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• pp.5331-5335
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• 2015

Purpose: The aim of this study was to compare the tumor-free and overall survival rates between patients with low-risk endometrial cancer who underwent surgical staging and those who did not undergo surgical staging. Materials and Methods: Data, including demographic characteristics, grade of the tumor, myometrial invasion, cervical involvement, peritoneal washing, lymph node involvement, lymphovascular space invasion, postoperative complication, adjuvant treatment, cancer recurrence, and tumor-free and overall survival rates, for patients with low-risk endometrioid endometrial cancer who were treated surgically with and without pelvic and paraaortic lymph node dissection (LND) were analyzed retrospectively. The patients diagnosed with endometrioid endometrial cancer including the following criteria were considered low-risk: 1) a grade 1 (G1) or grade 2 (G2) endometrioid histology; 2) myometrial invasion of <50% upon magnetic resonance imaging (MRI); 3) no stromal glandular or stromal invasion upon MRI; and 4) no evidence of intra-abdominal metastasis. Then the patients at low-risk were divided into two groups; group 1 (n=117): patients treated surgically with pelvic and paraaortic LND and group 2 (n=170): patients treated surgically without pelvic and paraaortic LND. Results: There was no statistical significance when the groups were compared in terms of lymphovascular space invasion, cervical involvement, positive cytology, and recurrence, whereas the administration of an adjuvant therapy was higher in group 2 (p<0.005). The number of patients with positive pelvic nodes and the number of metastatic pelvic nodes were significantly higher in the group with positive LVI than in the group without LVI (p<0.005). No statistically significant differences were detected between the groups in terms of tumor-free survival (p=0.981) and overall survival (p=0.166). Conclusions: Total hysterectomy with bilateral salpingo-oophorectomy and stage-adapted postoperative adjuvant therapy without pelvic and/or paraaortic lymphadenectomy may be safe and efficient treatments for low-risk endometrial cancer.

• 대한수의학회지
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• 제43권4호
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• pp.551-554
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• 2003

Nitric oxide synthase (NOS) has been reported in uterus. We examined the expression of the NOS isoforms, constitutive endothelial (eNOS) and inducible NOS (iNOS), in bovine uterus by immunohistochemistry. eNOS immunoreactivity was localized predominantly to the endothelial cells that line uterine microvessels and to endometrial glandular epithelial cells, but was barely detectable in endometrial stromal cells. iNOS immunostaining was detected in glandular epithelial and stromal cells in the endometrium and in the endothelial cells of myometrial blood vessels. These findings suggest that both eNOS and iNOS may play important roles in the physiology of the uterus, possibly by generating NO.

• Applied Microscopy
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• 제12권1호
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• pp.57-68
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• 1982

Cyclical changes in the fine structures of endometrial stroma of guinea pig during the estrous cycle were studied by electron microscopy. Cytochemical studies were made in order to investigate the ultrastructural localization of the acid phosphatase,alkaline phosphatase and ATPase in these cells. The results obtained are as follows: 1. During estrus collagen fibers were most abundant in the stroma. The stromal cells showed increases in the number of several cytoplasmic organelles, especially the rough endoplasmic reticulum was significantly increased and the structures were greatly differentiated. 2. Many cytoplasmic processes and cell debris have been distributed in the stroma of metestrus. The distributions were increased and degenerated mitochondria were observed during diestrus. 3. Cytochemical studies indicated that during metestrus and diestrus acid phosphatase activities were localized in the degenerating collagen fibers. Alkaline phosphatase activities were weak in the collegen fibers during proestrus and estrus which intense activities were localized around the cell membrane during metestrus and diestrus. ATPase activities were present on the cell membrane and intercellular space of stromal cell during proestrus and estrus.

• 대한암한의학회지
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• 제16권2호
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• pp.1-8
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• 2011

Background : Approximately 50% of patients with low-grade endometrial stromal sarcoma (LGESS) develops recurrent disease, mainly in lung or pelvis. Peritoneal metastasis of LGESS is an extremely rare phenomenon. Optimal treatment for metsatatic LGESS has not been established. Case : A 43-year-old woman had been diagnosed with LGESS with aortocaval lymphadenopathy. Despite of surgical resection, adjuvant radiation, chemotherapy and hormonal therapy, multiple lung and peritoneal metastasis developed after 15 months from initial treatment. Additional chemotherapy was done, but disease progressed. She had treatment with the allergen-removed Rhus verniciflua Stokes (aRVS) from November 2010 to May 2011. About 5 months to progression was observed. Conclusion : We suggests that aRVS could be an alternative treatment option for the metastatic LGESS patients. Further clinical studies on the efficacy of aRVS against metastatic LGESS are needed.

• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.881-887
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• 2015

Purpose: To analyze treatment modalities and prognostic factors in patients with Stage I-II endometrial stromal sarcoma (ESS). Materials and Methods: Twenty four patients (nineteen with low-grade ESS [LGESS] and five with high-grade ESS [HGESS]) were assessed retrospectively in terms of general characteristics, prognostic factors, treatment methods and survival. Results: Twenty patients were at Stage I and three were at Stage II. The stage of one patient could not be determined. With respect to age and comorbidity, no statistically significant difference was found among disease-free survival (DFS) (p=0.990; p=0.995). However, DFS was significantly shorter in Stage II than Stage I patients (p=0.002). It was also significantly shorter in HGESS patients than in LGESS patients (p=0.000). There was no statistically significant differences among the overall survival (OVS) times of patients with respect to age at diagnosis and comorbid disease (p=0.905; p=0.979) but OVS was significantly shorter in patients with HGESS (p=0.00) and Stage II disease (p=0.001). No statistically significant difference was found with respect to OVS between patients who received radiotherapy (RT) and those who did not receive RT (p=0.055). It was not statistically possible to include other treatment modalities in the analysis because of the small sample size. Conclusions: Grade and stage of a tumour were found to be the most important prognostic factors. It was not possible to determine the optimal surgical method and the effect of adjuvant treatment since the number of cases was insufficient.

• Tuberculosis and Respiratory Diseases
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• 제76권3호
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• pp.131-135
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• 2014

Low-grade endometrial stromal sarcoma (ESS) is an uncommon gynecologic malignancy of mesodermal origin. Pulmonary metastasis of low-grade ESS can occur years and decades after the treatment of the primary disease. Low-grade ESS is frequently mistaken as benign uterine neoplasm like uterine leiomyoma, which can potentially lead to a misdiagnosis. We present a case of a 42-year-old woman with low-grade ESS, that initially presented as an incidental lung mass with multiple pulmonary nodules, seven years after an uterine myomectomy. A $6.9{\times}5.8cm-sized$ intrapelvic mass suspected of uterine origin was discovered while searching for potential extrathoracic primary origin. A pelviscopy and simultaneous thoracoscopic lung biopsy were conducted for pathologic diagnosis. Finally, the diagnosis was confirmed as low-grade ESS with lung metastasis based on the histopathologic examination with immunohistochemical stain, which was showed positive for CD10 and hormone receptor markers (estrogen and progesterone receptors) in both pelvic and lung specimens.