• 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.

• Experimental and Molecular Medicine
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• v.50 no.12
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• pp.9.1-9.12
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• 2018

Endometriosis is a disease characterized by implants of endometrial tissue outside the uterine cavity and is strongly associated with infertility. Focal adhesion of endometrial tissue to the peritoneum is an indication of incipient endometriosis. In this study, we examined the effect of various cytokines that are known to be involved in the pathology of endometriosis on endometrial cell adhesion. Among the investigated cytokines, transforming growth factor-${\beta}1$ ($TGF-{\beta}1$) increased adhesion of endometrial cells to the mesothelium through induction of ${\alpha}2-6$ sialylation. The expression levels of ${\beta}$-galactoside ${\alpha}2-6$ sialyltransferase (ST6Gal) 1 and ST6Gal2 were increased through activation of $TGF-{\beta}RI/SMAD2/3$ signaling in endometrial cells. In addition, we discovered that terminal sialic acid glycan epitopes of endometrial cells engage with sialic acid-binding immunoglobulin-like lectin-9 expressed on mesothelial cell surfaces. Interestingly, in an in vivo mouse endometriosis model, inhibition of endogenous sialic acid binding by a $NeuAc{\alpha}2-6Gal{\beta}1$-4GlcNAc injection diminished $TGF-{\beta}1$-induced formation of endometriosis lesions. Based on these results, we suggest that increased sialylation of endometrial cells by $TGF-{\beta}1$ promotes the attachment of endometrium to the peritoneum, encouraging endometriosis outbreaks.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.4905-4908
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• 2015

Background: Platelets are blood elements thought to play a role in the immune system and therefore tumor development and metastasis. Platelet activation parameters such as mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) can be easily evaluated with the whole blood count and have been studied as markers of systemic inflammatory responses in various cancer types. Our aim in this study was to evaluate the correlation between endometrial pathologies and MPV, PDW and PCT. Materials and Methods: A total of 194 patients who presented to our clinic with abnormal vaginal bleeding were included in our study. The patients were divided into 3 groups (endometrial hyperplasia, endometrial cancer, control) according to their pathology results. The groups were compared for MPV, PDW, and PCT values obtained from the blood samples taken on endometrial biopsy day. Results: The endometrial cancer patients were the oldest group (p=0.04). There was no significant difference between the three groups in terms of white blood cell count (WBC), platelet count (PC), and hemoglobin (Hb) level. The highest MPV (p<0.001), PDW (p=0.002), and PCT (p<0.001) levels were in the endometrial cancer group, and the lowest levels were in the control group. Conclusions: The easy evaluation of platelet parameters in patients who are suspected of having endometrial pathology is a significant advantage. We found MPV, PDW, and PCT to be correlated with the severity of endometrial pathology with the highest values in endometrial cancer. Studies to be conducted together with different laboratory parameters will further help evaluate the diagnosis and severity of endometrial cancer and precursor lesions.

• Journal of Ginseng Research
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• v.45 no.1
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• pp.126-133
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• 2021

Background: 20(S)-protopanaxadiol (20(S)-PPD), one of the aglycone derivatives of major ginsenosides, has been shown to have an anticancer activity toward a variety of cancers. This study was initiated with an attempt to evaluate its anti-cancer activity toward human endometrial cancer by cell and xenograft mouse models. Methods: Human endometrial cancer (HEC)-1A cells were incubated with different 20(S)-PPD concentrations. 20(S)-PPD cytotoxicity was evaluated using MTT assay. Apoptosis was detected using the annexin V binding assay and cell cycle analysis. Cleaved poly (ADP-ribose) polymerase (PARP) and activated caspase-9 were assessed using western blotting. HEC-1A cell tumor xenografts in athymic mice were generated by inoculating HEC-1A cells into the flank of BALB/c female mice and explored to validate 20(S)-PPD anti-endometrial cancer toxicity. Results: 20(S)-PPD inhibited HEC-1A cell proliferation in a dose-dependent manner with an IC50 value of 3.5 μM at 24 h. HEC-1A cells morphologically changed after 20(S)-PPD treatment, bearing resemblance to Taxol-treated cells. Annexin V-positive cell percentages were 0%, 10.8%, and 58.1% in HEC-1A cells when treated with 0, 2.5, and 5 μM of 20(S)-PPD, respectively, for 24 h. 20(S)-PPD subcutaneously injected into the HEC-1A cell xenograft-bearing mice three times a week for 17 days manifested tumor growth inhibition by as much as 18% at a dose of 80 mg/kg, which sharply contrasted to controls that showed an approximately 2.4-fold tumor volume increase. These events paralleled caspase-9 activation and PARP cleavage. Conclusion: 20(S)-PPD inhibits endometrial cancer cell proliferation by inducing cell death via a caspase-mediated apoptosis pathway. Therefore, the 20(S)-PPD-like ginsenosides are endowed with ample structural information that could be utilized to develop other ginsenoside-based anticancer agents.

• Clinical and Experimental Reproductive Medicine
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• v.49 no.4
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• pp.259-269
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• 2022

Objective: Animal-free scaffolds have emerged as a potential foundation for consistent, chemically defined, and low-cost materials. Because of its good potential for high biocompatibility with reproductive tissues and well-characterized scaffold design, we investigated whether polyglycolic acid (PGA) could be used as an animal-free scaffold instead of natural fibrin-agarose, which has been used successfully for three-dimensional human endometrial cell culture. Methods: Isolated primary endometrial cells was cultured on fibrin-agarose and PGA polymers and evaluated various design parameters, such as scaffold porosity and mean fiber diameter. Cytotoxicity, scanning electron microscopy (SEM), and immunostaining experiments were conducted to examine cell activity on fabricated scaffolds. Results: The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay and SEM results showed that endometrial cells grew and proliferated on both scaffolds. Immunostaining showed cytokeratin and vimentin expression in seeded cells after 7 days of culture. On both scaffolds, an epithelial arrangement of cultured cells was found on the top layer and stromal arrangement matrix on the bottom layer of the scaffolds. Therefore, fibrin-agarose and PGA scaffolds successfully mimicked the human endometrium in a way suitable for in vitro analysis. Conclusion: Both fibrin-agarose and PGA scaffolds could be used to simulate endometrial structures. However, because of environmental and ethical concerns and the low cost of synthetic polymers, we recommend using PGA as a synthetic polymer for scaffolding in research instead of natural biomaterials.

• Journal of Embryo Transfer
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• v.11 no.3
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• pp.217-223
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• 1996

This study was conducted to investigate the effects of co-culture for the development rate to morula /blastocyst stages of early porcine embryos, derived from oocytes matured and fertilized in vitro, with porcine endometrial cell monolayers(PEM) in the two different media, respectively. The rates of embryos developed to 2-, 4-, 8~16-cell and morula /blastocyst stage were 49.6, 40.5, 28.2 and 15.3% in Ham's F-10 with PEM, and 55.3, 45.9, 32.7, and 17.6% in TCM-HEPES with PEM, respectively. The above development rates to morula /blastocyst stages were significantly higher than those of the embryos cultured in the Ham's F-10 and TGM-HEPES without PEM(P<0.05). The in vitro development rates to the morula /blastocyst stage of 1-cell embryos cultured in Ham's F-10 and TCM-HEPES without PEM were 0~1.2%. Especially, most of embryos were observed to arrest the development beyond 4-cell stages. As shown in the above results, the co-culture of in vitro produced porcine embryos with PEM in the two different media enhanced the development of fertilized eggs to morula /blastocyst stages in vitro. However, we didn't find out any differences for the in vitro development to morula /blastocyst stages between Ham's F-10 and TcM-HEPES media.

• Journal of Ginseng Research
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• v.44 no.1
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• pp.96-104
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• 2020

Objectives: Oleanolic acid, a minor element of ginsenosides, and its derivatives have been shown to have cytotoxicity against some tumor cells. The impact of cytotoxic effect of oleanolic acid 3-acetate on ovarian cancer SKOV3 cells and endometrial cancer HEC-1A cells were examined both in vivo and in vitro to explore the underlying mechanisms. Methods: Cytotoxic effects of oleanolic acid 3-acetate were assessed by cell viability, phosphatidylserine exposure on the cell surface, mitochondrial release of cytochrome C, nuclear translocation of apoptosis-inducing factor, depolarization of mitochondrial transmembrane potential (∆Ψ_m), and generation of reactive oxygen species (ROS). In vivo inhibition of tumor growth was also assessed with xenografts in immunocompromised mice. Results: Oleanolic acid 3-acetate exhibited potent cytotoxicity toward SKOV3 and HEC-1A cells by decreasing cell viability in a concentration-dependent manner. Importantly, oleanolic acid 3-acetate effectively suppressed the growth of SKOV3 cell tumor xenografts in immunocompromised mice. Furthermore, oleanolic acid 3-acetate induced apoptotic cell death as revealed by loss of ∆Ψ_m, release of cytochrome c, and nuclear translocation of apoptosis-inducing factor with a concomitant activation of many proapoptotic cellular components including poly(ADP-ribose) polymerase, Bcl-2, and caspases-8, caspase-3, and caspase-7. Oleanolic acid 3-acetate, however, caused a decrease in ROS production, suggesting the involvement of an ROS-independent pathway in oleanolic acid 3-acetate-induced apoptosis in SKOV3 and HEC-1A cells. Conclusion: These findings support the notion that oleanolic acid 3-acetate could be used as a potent anticancer supplementary agent against ovarian and endometrial cancer. Oleanolic acid 3-acetate exerts its proapoptotic effects through a rather unique molecular mechanism that involves an unconventional ROS-independent but mitochondria-mediated pathway.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2004.05a
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• pp.145-145
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• 2004

• The Korean Journal of Cytopathology
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• v.11 no.1
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• pp.1-10
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• 2000

The purpose of this study is to describe the cellular characteristics of endometrial hyperplasia without/with atypia in cervical smears. These cellular features were compared with those of normal endometrium and endometrial carcinoma. We reviewed 265 cervical smears : 64 normal proliferative endometrium, 118 endometrial hyperplasia without atypia, 21 endometrial hyperplasia with atypia, and 62 endometrial adenocarcinoma. Of these smears, 72(27.2%) smears which had diagnostic endometrial epithelial cells were selected for this study. The cytologic abnormalities about cellularity, background, changes in cellular architecture, alterations in nuclear size, anisokaryosis, chromatin pattern, nucleoli, cytoplasmic vacuoles, and mitosis were observed. Nuclear enlargement(1.6 to 2 times of the nucleus in the intermediate squamous cell) and anisokaryosis(${\geq}$2 fold in size variation) were highly suggestive of endometrial hyperplasia without/with atypia. The nuclei from endometrial hyperplasia with atypia were more coarsely granular in chromatin patterns than hyperplasia without atypia(33.3% vs 3.4%). Micronucleoli were observed in all endometrial conditions, but the presence of macronucleoli were more suggestive of hyperplasia with atypia(22.2%) and adenocarcinoma(55%). The changes in cellular architecture(loss of polarity, uneven internuclear distance, overlapping and loose arrangement) were seen in hyperplasia with atypia and adenocarcinoma. Characteristically, bloody background was seen in endometrial hyperpiasia, and cellular detritus or granular proteinaceous material was only observed in endometrial adenocarcinoma. Mitoses were also observed in adenocarcinoma. In conclusion, although there is no single parameter useful for the cytologic differential diagnosis of endometrial lesions, combined cytologic evaluation can be used to diagnose hyperplasia cytologically.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5659-5663
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• 2012

To investigate the expression of hPOT1 in the HeLa cell line and screen point mutations of hpot1 in different tumor tissues a two step osmotic method was used to extract nuclear proteins. EMSA was performed to determine the expression of hPOT1 in the HeLa cell line. PCR was also employed to amplify the exon14 sequence of the hpot1 gene in various of cancer tissues. A SV gel and PCR clean-up system was performed to enrich PCR products. DNAStar was used to analyse the exon14 sequence of the hpot1 gene. hPOT1 was expressed in the HeLa cell line and the signal was gradually enhanced as the amount of extracted nuclear proteins increased. The DNA fragment of exon14 of hpot1 was successfully amplified in the HeLa cell line and all cancer tissues, point mutations being observed in 2 out of 3 cases of endometrial cancer (66.7%) despite the hpot1 sequence being highly conserved. However, the sequence of hpot1 exon14 do not demonstrate point mutations in most cancer tissues. Since hPOT1 was expressed in HeLa cell and the probability of gene point variants was obviously higher in endometrial cancer than other cancers, it may be involved in the pathogenesis of gynecological cancers, especially in cervix and endometrium.