• IMMUNE NETWORK
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• v.23 no.2
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• pp.14.1-14.14
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• 2023

Immune status including the immune cells and cytokine profiles has been implicated in the development of endometriosis. In this study, we analyzed Th17 cells and IL-17A in peritoneal fluid (PF) and endometrial tissues of patients with (n=10) and without (n=26) endometriosis. Our study has shown increased Th17 cell population and IL-17A level in PF with endometriosis patients. To determine the roles of IL-17A and Th17 cells in the development of endometriosis, the effect of IL-17A, major cytokine of Th17, on endometrial cells isolated from endometriotic tissues was examined. Recombinant IL-17A promoted survival of endometrial cells accompanied by increased expression of anti-apoptotic genes, including Bcl-2 and MCL1, and the activation of ERK1/2 signaling. In addition, treatment of IL-17A to endometrial cells inhibited NK cell mediated cytotoxicity and induced HLA-G expression on endometrial cells. IL-17A also promoted migration of endometrial cells. Our data suggest that Th17 cells and IL-17A play critical roles in the development of endometriosis by promoting endometrial cell survival and conferring a resistance to NK cell cytotoxicity through the activation of ERK1/2 signaling. Targeting IL-17A has potential as a new strategy for the treatment of endometriosis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9603-9606
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• 2014

Background: Endometrial cancer is the fourth most common cancer among women in developed countries. Patients with endometrial cancer may benefit from systemic chemotherapy alone or in combination with targeted therapies if the disease is clinically diagnosed prior to spread and metastasis to other organs. The aim of this study was to evaluate the prognostic role of p53 polymorphism and its correlation with tumor grade in human uterine endometrial carcinomas. Materials and Methods: A total of 75 patients with endometrial carcinomas were studied for possible mutations in exon 4 of the p53 gene using polymerase chain reaction and restricting fragment length polymorphism techniques and sequencing. Results: In recent study, The rate of homozygote genotype of pro/pro or Arg/Arg in high grade group was higher than in comparison with low grade one. In addition samples that were undigested in RFLP, showed mutation in exone 4. Conclusions: Our findings showed that high grade endometrial carcinomas are highly associated with TP53 polymorphisms in comparison with low grades.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6789-6794
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• 2015

Background: To analyze the expression of estrogen receptors (ER), progesterone receptors (PR), C-erbB-2 and Ki-67 in endometrial carcinoma (EC) and their relationships with the clinicopathological features. Materials and Methods: Sixty-seven EC samples, 53 normal endometrial samples and 53 atypical hyperplasia endometrial samples were all selected in Shaanxi Provincial People's Hospital from Jun., 2012 to Jun., 2014. The expression of ER, PR, C-erbB-2 and Ki-67 in EC tissue, normal endometrial tissue and atypical hyperplasia endometrial tissue was respectively detected using immunohistochemical SP method. The relationships between the expression of ER, PR, C-erbB-2 and Ki-67 and the patients' clinicopathological features as well as their correlations in EC tissue were also analyzed. Results: The positive expression rates of ER and PR in EC tissue were 44.8% and 41.8%, respectively, dramatically lower than in atypical hyperplasia endometrial tissue and normal endometrial tissue (P<0.01). The positive expression rates of C-erbB-2 and Ki-67 in EC tissue were 80.6% and 64.2%, respectively, significantly higher than in atypical hyperplasia endometrial tissue and normal endometrial tissue (P<0.01). In EC tissue, the expression of ER and PR was closely associated with the differentiated degrees and depth of myometrial invasion (P<0.05), while that of C-erbB-2 and Ki-67 with the clinical staging, differentiated degrees, depth of myometrial invasion and presence or absence of lymph node metastasis (P<0.05). Spearman correlation analysis further displayed that the expression of ER was positively correlated with PR (r=0.393, P=0.001), but negatively with C-erbB-2 and Ki-67 (r=-0.469, P=0.000; r=-0.329, P=0.007); The expression of PR was negatively correlated with C-erbB-2 and Ki-67 (r=-0.273, P=0.025; r=-0.251, P=0.041), but that of C-erbB-2 positively with Ki-67 (r=0.342, P=0.005). Conclusions: Abnormal expression of ER, PR, C-erbB2 and Ki-67 might play an important role in endometrial malignant transformation and cell differentiation, so their joint detection is likely to be a comprehensive combination of immune factors, which is of great importance for EC prognosis.

• Clinical and Experimental Reproductive Medicine
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• v.30 no.1
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• pp.15-21
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• 2003

Objective : Clomiphene citrate is one of the most commonly used drugs in the treatment of infertility, but the pregnancy rate achieved with clomiphene citrate is significantly lower than the ovulation rate due to its antiestrogenic effect on the endometrium. Endometrial prolactin is considered to be a marker and an inducer of predecidualization that is characteristic of secretory endometrium. The purpose of this study was to evaluate the association of clomiphene citrate and unsatisfactory endometrial differentiation to secretory endometrium by examining the endometrial expression of prolactin in clomiphene citratetreated infertile women with luteal phase defect. Methods : The endometrial samples from infertile women with luteal phase defect (n=27) were examined. Five cases during secretory phase and six cases during proliferative phase were obtained by biopsy. Sixteen cases were obtained by biopsy during secretory phase after clomiphene citrate treatment. By immunohistochemical staining for prolactin, all obtained endometrial tissues were examined. The differences in the endometrial expression of prolactin were evaluated between proliferative phase and secretory phase, and between clomiphene citrate treated group and no treatment group during secretory phase. Results: The staining of endometrial prolactin was significantly more intense in the glandular epithelial cells and stromal cells in the secretory endometrium than in the proliferative endometrium. The glandular expression of prolactin in the secretory endometrium was not significantly different between the clomiphene citrate-treated group and no treatment group (p=0.719), but the staining of prolactin in the stromal cells was significantly less intense in the clomiphene citrate-treated group than no treatment group (p=0.019). Conclusion: In this investigation, we demonstrated that the endometrial stromal expression of prolactin in the secretory phase was significantly lower in the clomiphene citrate-treated group campared with no treatment group in infertile women with luteal phase defect. And our finding suggests that clomiphene citrate may have an adverse effect on the endometrial predecidualization in infertile women.

• BMB Reports
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• v.50 no.8
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• pp.429-434
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• 2017

Endometriosis is the abnormal growth of endometrial cells outside the uterus, causing pelvic pain and infertility. Furthermore, adhesion of endometrial tissue fragments to pelvic mesothelium is required for the initial step of endometriosis formation outside uterus. $TGF-{\beta}1$ and adhesion molecules importantly function for adhesion of endometrial tissue fragments to mesothelium outside uterus. However, the function of $TGF-{\beta}1$ on the regulation of adhesion molecule expression for adhesion of endometrial tissue fragments to mesothelium has not been fully elucidated. Interestingly, transforming growth factor ${\beta}1$ ($TGF-{\beta}1$) expression was higher in endometriotic epithelial cells than in normal endometrial cells. The adhesion efficiency of endometriotic epithelial cells to mesothelial cells was also higher than that of normal endometrial cells. Moreover, $TGF-{\beta}1$ directly induced the adhesion of endometrial cells to mesothelial cells through the regulation of integrin of ${\alpha}V$, ${\alpha}6$, ${\beta}1$, and ${\beta}4$ via the activation of the $TGF-{\beta}1/TGF-{\beta}RI/Smad2$ signaling pathway. Conversely, the adhesion of $TGF-{\beta}1-stimulated$ endometrial cells to mesothelial cells was clearly reduced following treatment with neutralizing antibodies against specific $TGF-{\beta}1-mediated$ integrins ${\alpha}V$, ${\beta}1$, and ${\beta}4$ on the endometrial cell membrane. Taken together, these results suggest that $TGF-{\beta}1$ may act to promote the initiation of endometriosis by enhancing integrin-mediated cell-cell adhesion.

• Journal of Yeungnam Medical Science
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• v.16 no.2
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• pp.296-301
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• 1999

Background: Generally, it is difficult to differentiate uterine malignant mixed M$\ddot{u}$ llerian tumor(MMMT) from endometrial carcinom in radiological and clinical aspects. Our purpose is to investigate MR findings that distinguishes MMMT from endometrial carcinoma. Materials and Methods: We retrogradely evaluated the magnetic resonance imaging findings of pathologically proven 5 cases of malignant mixed M$\ddot{u}$llerian tumor(MMMT) and 14 endometrial carcinomas to know the differential points of these two tumors originating in the endometrial cavity. The size of the mass, presence or absence of myometrial or uterine cervical invasion, growth pattern of the mass, signal intensity and degree and pattern of contrast enhancement were analyzed and compared. Results: The length of the long axis of the MMMT was 1.5-9.0cm(average, 5.7cm) but that of the endometrial carcinoma was 0.5-6.0cm(average, 2.5cm). Invasion of uterine cervix which was found in 3 MMMT cases, dilated the endometrial cavity and the lumen of the uterine cervix and showed the pattern of growing into the external os. Invasion of uterine cervix was found in only one case of endometrial carcinoma. The presence or absence of myometrial invasion, the signal intensity and homogeneity on T1- and T2-weighted images, and the degree and patterns of contrast enhancement showed no significant difference. Conclusion: Any specific finding to differentiate MMMT from endometrial carcinoma was not ascertained. However, MMMT can be suspected if the size of the endometrial mass is greater than 5cm and if the mass dilates the enocervical canal and invades the uterine cervix.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1689-1692
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• 2014

Background: An easy, reproducible and simple marker is needed to estimate phase of endometrial pathologic lesions such as hyperplasia and endometrial cancer and distinguish from pathologically normal results. We here aimed to clarify associations among neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), endometrial hyperplasia and cancer in patients with abnormal uterine bleeding. Materials and Methods: Patients (n=161) who were admitted with abnormal uterine bleeding and the presence of endometrial cells on cervical cytology or thick endometrium were investigated. The study constituted of three groups according to pathologic diagnosis. Group 1 included endometrial precancerous lesions like hyperplasia (n=63), group 2 included endometrial cancerous lesions (n=38) and group 3 was a pathologically normal group (n=60). Blood samples were obtained just before the curettage procedure and the NLR was defined as the absolute neutrophil count divided by the absolute lymphocyte count; similarly, PLR was defined as the absolute platelet count divided by the absolute lymphocyte count. Results: The white blood cell count was significantly higher in patients with cancer than in those with hyperplasia (p=0.005). The platelet count and neutrophil to lymphocyte ratio were significantly higher in patients with cancer than in control patients, but there was significantly no difference between patients with hyperplasia and other groups (p=0.001 and p=0.025 respectively). PLR was significantly lower in control subjects than in other groups (p<0.001), but there was no significant difference between patients with hyperplasia and those with cancer. Conclusions: PLR was significantly lower in control subjects than in other groups. Thus both hyperplasia and cancer may be differentiated from pathologically normal patients by using PLR. White blood cell count was significantly higher in patients with cancer than in those with hyperplasia and pathologically normal patients. Therefore white blood cell count may be used for discriminate hyperplasia to cancer. By using multiple inflammation parameters, discrimination may be possible among endometrial cancer, endometrial precancerous lesions and pathologically normal patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5355-5358
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• 2014

Background: To assess the role of sonographic endometrial thickness and hysteroscopic polyp size in predicting premalignant and malignant polyps in postmenopausal women. Materials and Methods: A total of 328 postmenopausal women with abnormal uterine bleeding and thickened endometrium underwent operative hysteroscopy due to detection of endometrial polyps were included in this retrospective study. Preoperative endometrial thickness measured by transvaginal ultrasonography and polyp size on hysteroscopy were noted. Hysteroscopic resection with histology was performed for endometrial polyps. Endometrial thickness and polyp size were evaluated on the basis of final diagnosis established by histologic examination. Receiver operator characteristic curves were calculated to assess the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of endometrial thickness and polyp size for detecting pemalignant and malignant polyps. Results: Premalignant and malignant polyps were identified in 26 (7.9%) of cases. Sonographic measurement showed a greater endometrial thickness in cases of premalignant and malignant polyps when compared to benign polyps. On surgical hysteroscopy, premalignant and malignant polyps were also larger. Endometrial thickness demonstrated a sensitivity of 53.8%, specificity of 85.8%, PPV of 24.6% and NPV of 95.6% at a cut-off limit of 11.5 mm with diagnostic accuracy of 83.2%. Polyp size has a diagnostic accuracy of 94.8% with a sensitivity of 92.3%, specificity of 95.0%, PPV of 61.5% and NPV of 99.3% at a cut-off point of 19.5mm. Conclusions: Endometrial thickness measured by transvaginal ultrasonography is not sufficient in predicting premalignant and malignant endometrial polyps in postmenopausal women with abnormal uterine bleeding and thickened endometrium. Polyp size on hysteroscopy is a more accurate parameter, because of better sensitivity and specificity. However, while polyp size ${\geq}19.5mm$ seems to have a great accuracy for predicting premalignancy and malignancy, histologic evaluation is still necessary to exclude premalignant and malignant polyps.

• Korean Journal of Clinical Laboratory Science
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• v.49 no.4
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• pp.455-459
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• 2017

MicroRNAs (miRNAs/miRs) are a group of small noncoding RNAs that modulate gene expression. Many studies, demonstrating altered expressions of specific miRNAs in diverse types of human neoplasia, suggested that they may play a key role in tumorigenesis. Recently, miRNA genes were found to be abnormally expressed in several types of cancer, including endometrial cancer. However, miR-23b and miR-203 expression in endometrial cancer has yet to be studied in Korea. As such, the purpose of this study was to analyze miR-23b and miR-203 expressions in endometrial cancer and to evaluate the relationship between miR-23b and miR-203 expressions. A retrospective study was carried out on the formalin-fixed, paraffin-embedded tissues of 42 endometrial cancer tissues using quantitative real-time PCR. In endometrial cancer tissues, miR-23b expression levels ($2.70{\pm}4.45$) were higher than miR-203 expression levels ($-2.34{\pm}4.08$). Endometrial cancer tissues showed an overexpression of miR-23b in 30 (71.4%) of the 42 endometrial cancer cases, whereas miR-203 was underexpressed in 29 (69.0%) of the 42 cases. There was a significant association between miR-23b and miR-203 expressions in endometrial cancer tissues (p=0.0005). These findings suggest that miR-23b and miR-203 expressions may be involved in endometrial carcinogenesis. More studies are needed to further define the relationship between miR-23b and miR-203 expressions and tissue-specific protein expression.

• Asian-Australasian Journal of Animal Sciences
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• v.18 no.12
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• pp.1708-1714
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• 2005

Keratinocyte growth factor (KGF) functions in epithelial growth and differentiation in many tissues and organs. KGF is expressed in the uterine endometrial epithelial cells during the estrous cycle and pregnancy in pigs, and receptors for KGF (KGFR) are expressed by conceptus trophectoderm and endometrial epithelia. KGF has been shown to stimulate the proliferation and differentiation of conceptus trophectoderm. However, the role of KGF on the endometrial epithelial cells has not been determined. Therefore, this study determined the effect of KGF on proliferation and differentiation of endometrial epithelial cells in vitro and in vivo using an immortalized porcine luminal epithelial (pLE) cell line and KGF infusion into the uterine lumen of pigs between Days 9 and 12 of estrous cycle. Results showed that KGF did not stimulate proliferation of uterine endometrial epithelial cells in vitro and in vivo determined by the $^3$H]thymidine incorporation assay and the proliferating cell nuclear antigen staining, respectively. Effects of KGF on expression of several markers for epithelial cell differentiation, including integrin receptor subunits $\alpha$4, $\alpha$5 and $\beta$1, plasmin/trypsin inhibitor, uteroferrin and retinol-binding protein were determined by RT-PCR, Northern and slot blot analyses, and immunohistochemisty, and KGF did not affect epithelial cell differentiation in vitro and in vivo. These results show that KGF does not induce epithelial cell proliferation and differentiation, suggesting that KGF produced by endometrial epithelial cells acts on conceptus trophectoderm in a paracrine manner rather than on endometrial epithelial cells in an autocrine manner.