Publications by authors named "Seob Jeon"

25 Publications

  • Page 1 of 1

Intracellular delivery of oxaliplatin conjugate via cell penetrating peptide for the treatment of colorectal carcinoma in vitro and in vivo.

Int J Pharm 2021 Sep 19;606:120904. Epub 2021 Jul 19.

Department of Electronic Materials and Devices Engineering, Soonchunhyang University, Asan 31538, Republic of Korea; Department of Chemical Engineering, Soonchunhyang University, Asan 31538, Republic of Korea. Electronic address:

Pt-based drugs are one of the main active agents in colorectal cancer treatment. However, drug resistance and dose-dependent side effects are the main barriers that restrict their clinical applications. As an alternative approach to these issues, we designed and synthesized a cell penetrating peptide (CPP) octaarginine-oxaliplatin conjugate that quickly and successfully delivered oxaliplatin into colon cancer cells. The CPP octaarginine is a well-studied cationic peptide that can play a role as a drug delivery vector. In this work, an octaarginine CPP (RRRRRRRR) was conjugated with oxaliplatin via a specific heterobifunctional linker. The in vitro studies showed the conjugate had affinity toward mitochondria inside cells and the MTT assay confirmed that conjugate is active in low micromolar range against colon cancer cells, requiring much lower concentrations than the oxaliplatin alone to reach IC. More importantly, in the in vivo mouse study, the conjugate effectively inhibited tumor growth and showed considerably high antitumor activity, demonstrating the conjugate can perform well in vivo. This strategy may offer a new approach for designing oxaliplatin derivatives or prodrugs with remarkable therapeutic capabilities.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120904DOI Listing
September 2021

Real-World Experience of Pembrolizumab Monotherapy in Patients with Recurrent or Persistent Cervical Cancer: A Korean Multi-Center Retrospective Study (KGOG1041).

Cancers (Basel) 2020 Oct 29;12(11). Epub 2020 Oct 29.

Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul 03722, Korea.

This study investigated the antitumor activity and safety of pembrolizumab in patients with recurrent cervical cancer in real-world practice. We conducted a multi-center retrospective study of patients with recurrent or persistent cervical cancer treated with pembrolizumab at sixteen institutions in Korea between January 2016 and March 2020. The primary endpoints were the objective response rate (ORR) and safety. Data were available for 117 patients. The median age was 53 years (range, 28-79). Sixty-four (54.7%) patients had an Eastern Cooperative Oncology Group (ECOG) performance status of ≥2. Forty-nine (41.9%) patients were stage ≥III at diagnosis. Eighty-eight (75.2%) patients had squamous cell carcinoma. The median number of prior chemotherapy lines was two (range, 1-6). During the median follow-up of 4.9 months (range, 0.2-35.3), the ORR was 9.4%, with three complete responses and eight partial responses. The median time to response was 2.8 months (range 1.3-13.1), and the median duration of response (DOR) was not reached. In the population of patients with favorable performance status (ECOG ≤1) ( = 53), the ORR was 18.9%, and the median DOR was 8.9 months (range, 7.3-10.4). Adverse events occurred in 55 (47.0%) patients, including eight (6.8%) patients who experienced grade ≥3 events, and two of them were suspicious treatment-related deaths. Pembrolizumab had modest antitumor activity in patients with recurrent cervical cancer comparable to that found in previously reported clinical trials. However, in patients with favorable performance status, pembrolizumab showed effective antitumor activity. Some safety profiles should be carefully monitored during treatment.
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http://dx.doi.org/10.3390/cancers12113188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693862PMC
October 2020

Ovarian yolk sac tumor with epithelial tumor component in a postmenopausal woman - case report and literature review.

Int J Clin Exp Pathol 2020 1;13(9):2401-2406. Epub 2020 Sep 1.

Department of Pathology, College of Medicine, Soonchunhyang University Cheonan, Korea.

Ovarian yolk sac tumors are common germ cell tumors usually arising in young women. Yolk sac tumors in elderly women are infrequently encountered and most of them are combined with other epithelial tumor components including endometrioid carcinoma or serous carcinoma. Here, we report an extremely rare case of a yolk sac tumor with mucinous tumor and large cell neuroendocrine carcinoma components in a postmenopausal woman, which is the third yolk sac tumor case with a neuroendocrine tumor element in an elderly woman. An 82-year-old female visited our hospital due to abdominal distention. Abdominal computed tomography (CT) demonstrated a solid and cystic mass, measuring about 9.0 cm in the largest diameter. A total hysterectomy with bilateral salpingo-oophorectomy and excisional biopsy of the peritoneal metastatic lesions was performed. Histologic evaluation revealed a malignant ovarian tumor composed of a variety of tumor components, including a yolk sac tumor, a mucinous tumor with multifocal mucinous carcinomatous areas, and a large-cell neuroendocrine carcinoma. After surgery, the patient refused further treatment and the disease recurred in the pelvic peritoneum and a left supraclavicular lymph node nine months later.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539866PMC
September 2020

Green Synthesis, Characterization and Application of Natural Product Coated Magnetite Nanoparticles for Wastewater Treatment.

Nanomaterials (Basel) 2020 Aug 18;10(8). Epub 2020 Aug 18.

Department of Chemistry, Cooch Behar Panchanan Barma University, Vivekananda Street, Cooch Behar 736101, West Bengal, India.

Adsorption of organic pollutants, toxic metal ions, and removal of harmful bacteria can give us clean and pure drinkable water from wastewater resources. Respective magnetite nanoparticles (MNPs) were synthesized using a cheaper and greener way in an open-air environment with the use of crude latex of (JC) and leaf extract of (CT). Characterization of MNPs had been performed by dynamic light scattering (DLS), Ultraviolet-visible (UV-vis) spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, powdered X-ray diffraction (XRD), and field emission scanning electron microscope (FE-SEM). The size ranges of the synthesized MNPs were observed in between 20-42 nm for JC-FeO and within 26-35 nm for CT-FeO by FE-SEM images. The effect of synthesized magnetic nanoparticles in wastewater treatment (bacterial portion), dye adsorption, toxic metal removal as well as antibacterial, antioxidant, and cytotoxic activities were studied. This purification will lead to an increase in the resources of pure drinking water in the future.
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http://dx.doi.org/10.3390/nano10081615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466664PMC
August 2020

In Vivo and In Vitro Anticancer Activity of Doxorubicin-loaded DNA-AuNP Nanocarrier for the Ovarian Cancer Treatment.

Cancers (Basel) 2020 Mar 9;12(3). Epub 2020 Mar 9.

Department of Chemistry, Soonchunhyang University, Asan 31538, Korea.

In this study, we have determined the anticancer activity of doxorubicin (Dox)-loaded DNA/gold nanoparticle (AuNP) nanocarrier (Dox-DNA-AuNP) for the treatment of ovarian cancer. The anticancer effect of Dox-DNA-AuNP was evaluated in vitro using the EZ-Cytox cell viability assay on three human ovarian cancer cell lines, SK-OV-3, HEY A8, and A2780. Dox-DNA-AuNP exhibited outstanding activity with good IC values of 4.8, 7.4, and 7.6 nM for SK-OV-3, HEY A8, and A2780, respectively. In vivo evaluation further demonstrated the superior anticancer effects of Dox-DNA-AuNP by inhibiting tumor growth compared to free Dox in an established SK-OV-3 xenograft mice model. Dox-DNA-AuNP showed about a 2.5 times higher tumor growth inhibition rate than free Dox. Furthermore, the immunohistochemical analysis of Ki67 antigen expression showed the lowest number of proliferative cells in the ovarian tumor tissue treated with Dox-DNA-AuNP. These results suggest Dox-DNA-AuNP might be a potential effective agent in ovarian cancer chemotherapy.
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http://dx.doi.org/10.3390/cancers12030634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139456PMC
March 2020

Asian Society of Gynecologic Oncology International Workshop 2018.

J Gynecol Oncol 2019 Mar 14;30(2):e39. Epub 2019 Jan 14.

Department of Gynecology, Obstetrics and Gynecology, Hospital of Fudan University, Shanghai, China.

The Asian Society of Gynecologic Oncology International Workshop 2018 on gynecologic oncology was held in the Ajou University Hospital, Suwon, Korea on the 24th to 25th August 2018. The workshop was an opportunity for Asian doctors to discuss the latest findings of gynecologic cancer, including cervical, ovarian, and endometrial cancers, as well as the future of fertility-sparing treatments, minimally invasive/radical/debulking surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy. Clinical guidelines and position statement of Asian countries were presented by experts. Asian clinical trials for gynecologic cancers were reviewed and experts emphasized the point that original Asian study is beneficial for Asian patients. In Junior session, young gynecologic oncologists presented their latest research on gynecologic cancers.
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http://dx.doi.org/10.3802/jgo.2019.30.e39DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393643PMC
March 2019

Loss of RUNX3 is significantly associated with advanced tumor grade and stage in endometrial cancers.

Mol Med Rep 2018 Jun 23;17(6):8173-8179. Epub 2018 Apr 23.

Department of Obstetrics and Gynecology, Soonchunhyang University Cheonan Hospital, Cheonan, South Chungcheong 31151, Republic of Korea.

Loss of runt‑related transcription factor 3 (RUNX3) has been reported in various cancers, and one of the mechanisms mediating loss of RUNX3 expression is DNA methylation. However, the role of RUNX3 expression and its DNA methylation status as prognostic factors in endometrial cancer remain unclear. In the present study, the expression and promoter methylation of RUNX3 was examined in endometrial cancer tissues and cell lines, as well as their association with endometrial cancer prognosis. Fifty‑five endometrial cancer tissues and two endometrial cancer cell lines (HEC1‑α and Ishikawa) were studied. RUNX3 expression and promoter methylation were examined using reverse transcription‑polymerase chain reaction (RT‑PCR), methylation specific PCR (MS‑PCR), and immunohistochemical staining. The demethylating agent 5‑aza‑2'‑deoxycytidine (ADC) was used to reverse the methylation of the RUNX3 promoter. Loss of RUNX3 expression was observed in 50.9% (27/53) of endometrial cancer tissues and in the HEC1‑α cell line by immunohistochemistry and RT‑PCR, respectively. Methylation of the RUNX3 promoter was observed in 62.2% (33/53) of endometrial cancer tissues, 12.5% (1/8) of normal endometrial tissues, and the HEC1‑α cell line by MS‑PCR. Tumor grade and stage were significantly correlated with loss of RUNX3 expression. The expression of RUNX3 was restored by treatment with ADC and resulted in growth inhibition in HEC1‑α cells. The present results suggested that methylation may serve a critical role in the silencing of RUNX3 and loss of RUNX3 expression may serve as a prognostic marker in endometrial cancer.
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http://dx.doi.org/10.3892/mmr.2018.8915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983989PMC
June 2018

CORRIGENDUM: Correction of funding statement in ACKNOWLEDGEMENTS section: Epigenetic inactivation of in colorectal cancer.

Ann Surg Treat Res 2018 03 28;94(3):166. Epub 2018 Feb 28.

Department of Surgery, Soonchunhyang University College of Medicine, Cheonan, Korea.

[This corrects the article on p. 19 in vol. 94, PMID: 29333422.].
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http://dx.doi.org/10.4174/astr.2018.94.3.166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842091PMC
March 2018

Epigenetic inactivation of in colorectal cancer.

Ann Surg Treat Res 2018 Jan 28;94(1):19-25. Epub 2017 Dec 28.

Department of Surgery, Soonchunhyang University College of Medicine, Cheonan, Korea.

Purpose: Emerging evidence indicates that runt-related transcription factor 3 () is an important tumor suppressor gene in several cancer types, including colorectal cancer (CRC). However, the clinical significance of RUNX3 inactivation in CRC remains unclear. The aim of this study was to examine the correlation between clinicopathologic factors and RUNX3 hypermethylation/expression in CRC.

Methods: Sixty-two CRC patients who were treated at the Soonchunhyang University College of Medicine were recruited in this study. The hypermethylation of CpG islands in the RUNX3 promoter and the expression of RUNX3 mRNA were identified by methylation-specific polymerase chain reaction (PCR) and reverse transcriptase-PCR, respectively. The expression of RUNX3 was determined by immunohistochemical staining.

Results: Of the 62 CRC tissue samples, 20 (32.3%) presented hypermethylated RUNX3 promoters. Aberrant RUNX3 hypermethylation was found to be associated with vascular (P = 0.006) and lymphatic (P = 0.002) invasion. Hypermethylation of RUNX3 was associated with poor survival outcomes (P = 0.038). However, expression of RUNX3 was not a prognostic factor (P = 0.363).

Conclusion: Hypermethylation of RUNX3 may be a predictor of a poor prognosis in CRC.
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http://dx.doi.org/10.4174/astr.2018.94.1.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765274PMC
January 2018

Prognostic Value of Fluorine-18 Fluorodeoxyglucose Uptake of Bone Marrow on Positron Emission Tomography/Computed Tomography for Prediction of Disease Progression in Cervical Cancer.

Int J Gynecol Cancer 2017 05;27(4):776-783

*Department of Nuclear Medicine and †Institute for Integrative Medicine, Catholic Kwandong University College of Medicine, International St Mary's Hospital, Incheon, Korea; and Departments of ‡Obstetrics and Gynecology and §Nuclear Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Korea.

Objective: This study aimed to evaluate the prognostic value of fluorine-18 fluorodeoxyglucose (FDG) uptake of bone marrow (BM) on positron emission tomography (PET)/computed tomography in patients with uterine cervical cancer.

Methods: One hundred forty-five patients with cervical cancer who underwent staging FDG PET/computed tomography and subsequent surgical resection or chemoradiotherapy were retrospectively enrolled in the study. Mean BM FDG uptake (BM standardized uptake value [SUV]) and BM-to-liver uptake ratio of FDG uptake (BLR) were measured. Relationships of BM SUV and BLR with hematologic and inflammatory markers were evaluated. Prognostic values of PET parameters for predicting disease progression-free survival and distant recurrence-free survival (DRFS) were assessed with a Cox proportional hazards regression model.

Results: Bone marrow SUV and BLR were significantly correlated with white blood cell count and neutrophil-to-lymphocyte ratio. In the multivariate Cox regression analysis, International Federation of Gynecology and Obstetrics stage (P = 0.048), neutrophil-to-lymphocyte ratio (P = 0.028), platelet-to-lymphocyte ratio (PLR; P = 0.004), maximum SUV of cervical cancer (P = 0.030), and BLR (P = 0.031) were significantly associated with progression-free survival, whereas lymph node metastasis (P = 0.041), PLR (P = 0.002), and BLR (P = 0.025) were significantly associated with DRFS. In a patient subgroup with chemoradiotherapy, BLR (P = 0.044) was still an independent prognostic factor for predicting DRFS in multivariate analysis along with PLR (P = 0.004).

Conclusions: In patients with cervical cancer, BLR is associated with an increased risk of disease progression and distant recurrence.
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http://dx.doi.org/10.1097/IGC.0000000000000949DOI Listing
May 2017

Surgical manual of the Korean Gynecologic Oncology Group: ovarian, tubal, and peritoneal cancers.

J Gynecol Oncol 2017 Jan 22;28(1):e6. Epub 2016 Aug 22.

Department of Obstetrics and Gynecology, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea.

The Surgery Treatment Modality Committee of the Korean Gynecologic Oncology Group has determined to develop a surgical manual to facilitate clinical trials and to improve communication between investigators by standardizing and precisely describing operating procedures. The literature on anatomic terminology, identification of surgical components, and surgical techniques were reviewed and discussed in depth to develop a surgical manual for gynecologic oncology. The surgical procedures provided here represent the minimum requirements for participating in a clinical trial. These procedures should be described in the operation record form, and the pathologic findings obtained from the procedures should be recorded in the pathologic report form. Here, we describe surgical procedure for ovarian, fallopian tubal, and peritoneal cancers.
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http://dx.doi.org/10.3802/jgo.2017.28.e6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5165074PMC
January 2017

Management of Endometrial Hyperplasia With a Levonorgestrel-Releasing Intrauterine System: A Korean Gynecologic-Oncology Group Study.

Int J Gynecol Cancer 2016 May;26(4):711-5

*Departments of Obstetrics and Gynecology, CHA Gangnam Medical Center, CHA University; †Seoul National University College of Medicine, Seoul; ‡Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan; §Chonnam National University Medical School, Gwangju; ∥Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine, Seoul; ¶Gyeongsang National University School of Medicine, Jinju,; #Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul; **Inha University College of Medicine, Incheon; ††CHA Bundang Medical Center, CHA University, Bundang; ‡‡Ajou University School of Medicine, Suwon; §§Sanggye Paik Hospital, Inje University College of Medicine; and ∥∥Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.

Objective: The aim of the study was to evaluate the efficacy of the levonorgestrel intrauterine system (LNG-IUS) for treatment of endometrial hyperplasia (EH).

Methods: A prospective multicenter study was conducted from November 2010 to March 2014. Patients with histologically confirmed EH were treated with LNG-IUS. At 3, 6, and 9 months after LNG-IUS insertion, follow-up endometrial aspiration biopsies with the LNG-IUS in the uterus were undertaken. At the 12th month of follow-up, endometrial tissues were obtained via 2 methods: endometrial aspiration biopsy with the LNG-IUS in the uterus, followed by dilatation and curettage (D&C) after LNG-IUS removal. The primary outcome was the regression rate at 12 months after LNG-IUS insertion, and the secondary outcome was the consistency of the results between the endometrial aspiration biopsy and the D&C.

Results: The study population comprised 75 patients, including 37 with simple hyperplasia without atypia; 3 with atypical simple hyperplasia; 23 with complex hyperplasia without atypia, and 12 with atypical complex hyperplasia. Of these patients treated with the LNG-IUS, 38 (50.7%) were followed up at 12 months after LNG-IUS insertion. The complete regression rate at 12 months was 94.7% (36/38): 100% (6/6) of patients with atypical EH and 93.7% (30/32) with EH without atypia. In all of the cases (100%, 36/36), patients achieved complete regression within 3 months of LNG-IUS insertion. A comparison of the pathologic results from endometrial aspiration biopsy and D&C was carried out for 15 patients. In the histologic results by endometrial aspiration biopsy, 14 patients were diagnosed as "normal endometrium" and 1 as "insufficient tissue for pathologic evaluation." Among the 14 cases of normal endometrium by endometrial aspiration biopsy, 1 was diagnosed as "residual EH" by D&C, and the 1 case with insufficient tissue was diagnosed as normal endometrium by D&C.

Conclusions: Levonorgestrel intrauterine system is an effective and favorable method for treatment of EH.
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http://dx.doi.org/10.1097/IGC.0000000000000669DOI Listing
May 2016

Management of Endometrial Hyperplasia: A Survey of Members of the Korean Gynecologic Oncology Group.

Int J Gynecol Cancer 2015 Sep;25(7):1277-84

*Department of Obstetrics and Gynecology, CHA Gangnam Medical Center, CHA University; †Department of Obstetrics and Gynecology, Seoul National University Hospital; ‡Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University, Seoul; §Department of Obstetrics and Gynecology, Soonchunhyang University Cheonan Hospital, Cheonan; ∥Department of Obstetrics and Gynecology, Keimyung University, School of Medicine, Daegu; and ¶Department of Obstetrics and Gynecology, SMG-SNU Boramae Medical Center, Seoul, Korea.

Objectives: This study aimed to investigate the current management of endometrial hyperplasia (EH) in Korea.

Materials And Methods: This was an electronic survey, which included 40 questions, that was distributed to the members of the Korean Gynecologic Oncology Group in 2014.

Results: In total, 50 (69%) of 72 members responded to the survey. The oral progestogens were the most popular choices for managing EH without atypia (simple hyperplasia(SH), 64%; complex hyperplasia (CH), 52%). In the case of CH with atypia, most of the gynecologist respondents would perform hysterectomy (95.9%). For fertility preservation, the oral progestogens were the most popular choices (SH, 75.5%; CH, 56.3%), followed by the levonorgestrel-releasing intrauterine system (LNG-IUS). More than 70% of the respondents reported use of dilatation and curettage as a follow-up method.

Conclusions: Our survey results show that most of Korean gynecologic oncologists still prefer oral progestogens for conservative management of EH, notwithstanding the many successful reports on the LNG-IUS. As a follow-up evaluation method, dilatation and curettage is mostly used. To identify the optimum therapy, a randomized controlled trial comparing the LNG-IUS with continuous oral progestogens is required. Furthermore, a large-scale prospective study to confirm the most reliable technique for follow-up evaluation is necessary.
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http://dx.doi.org/10.1097/IGC.0000000000000483DOI Listing
September 2015

Pseudoaneurysm of uterine artery causing intra-abdominal and vaginal bleeding after cervical conization.

Obstet Gynecol Sci 2015 May 19;58(3):256-9. Epub 2015 May 19.

Department of Obstetrics and Gynecology, Soonchunhyang University Cheonan Hospital, Cheonan, Korea.

Uterine arterial pseudoaneurysm is a very rare condition usually associated with postpartum hemorrhage. It almost never occurs after cervical conization; however, since ruptured pseudoaneurysm could be life threatening, we should consider the possibility of vascular injury such as pseudoaneurysm when we find a patient with vaginal bleeding after the process of surgical operation. Emergency arterial embolization is a well established therapeutic option to control the ruptured pseudoaneurysm. This is a case report of uterine arterial pseudoaneurysm causing intra-abdominal bleeding followed by cervical conization, which was successfully treated by uterine artery embolization.
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http://dx.doi.org/10.5468/ogs.2015.58.3.256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4444524PMC
May 2015

A case of solitary fibrous tumor in the pelvis presenting massive hemorrhage during surgery.

Obstet Gynecol Sci 2015 Jan 16;58(1):73-6. Epub 2015 Jan 16.

Department of Pathology, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea.

Solitary fibrous tumors (SFTs) are unique soft-tissue tumors of submesothelial origin. These tumors are mainly located in the pleural space but they can be originated within a variety of sites, including the abdomen, the pelvis, the soft tissues and the retroperitoneum. SFTs from all sites are usually benign, and the surgical resection is curative in almost all cases. According to the review of literatures, during the surgical resection, massive hemorrhage could occur due to the hypervascular nature of SFTs. This is a case report on SFT in the pelvis presenting great vessel injury, which resulted in life threatening hemorrhage during the resection of tumor. We wish this paper alerts gynecologists about the risk of massive bleeding during the resection of tumor located at adjacent to great vessels in the pelvis.
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http://dx.doi.org/10.5468/ogs.2015.58.1.73DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303757PMC
January 2015

Clinical significance of a negative loop electrosurgical excision procedure biopsy in patients with biopsy-confirmed high-grade cervical intraepithelial neoplasia.

J Low Genit Tract Dis 2015 Apr;19(2):103-9

Objective: We sought to determine which clinical factors can predict this phenomenon and to better understand the clinical significance of negative loop electrosurgical excision procedure (LEEP) findings through long-term follow-up.

Methods: We identified 559 patients with biopsy-confirmed cervical intraepithelial neoplasia grade 2 or 3 (CIN 2, 3) who were treated by LEEP between February 2001 and December 2010. Preconization clinical characteristics, as well as high-risk human papillomavirus (hrHPV) status, were analyzed as possible predictors of an absence of a lesion in the specimen. The clinical significance of an absence of a lesion in the specimen, as well as other factors, was evaluated by Cox hazard regression analysis in terms of recurrence.

Results: No lesion on the LEEP specimen was found in 102 (18.2%) of 559 patients with CIN 2,3 on punch biopsy. Punch biopsy status of CIN 2, low HPV viral load (<100 relative light units [RLU]), and negative or positive HPV infection other than type 16 were significantly related to no lesion in the LEEP specimen. Postoperative HPV persistence (≥10 RLU) and same-type HPV detection were significantly related to recurrent disease of CIN 2+ (p < .001). The recurrence of patients with no lesion in LEEP did not statistically differ from that of patients with a lesion in the LEEP specimen (p = .390).

Conclusions: The absence of a lesion in the LEEP specimen is very common. A negative LEEP is associated with a persistence/recurrence rate similar to that of positive LEEP. We recommend that the follow-up for patients with no lesion in the LEEP specimen should be the same as that for patients with a lesion.
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http://dx.doi.org/10.1097/LGT.0000000000000061DOI Listing
April 2015

Multicystic benign mesothelioma of the pelvic peritoneum presenting as acute abdominal pain in a young woman.

Obstet Gynecol Sci 2013 Mar 12;56(2):126-9. Epub 2013 Mar 12.

Department of Obstetrics and Gynecology, Soonchunhyang University Cheonan Hospital, Cheonan, Korea.

Multicystic benign mesothelioma (MBM) of the peritoneum is a very rare condition. Since the first description of MBM in 1979, approximately 100 cases have been reported. This is a case report of MBM of the pelvic peritoneum presenting as acute abdominal pain in a young woman. Laparoscopy confirmed multiple grapelike clusters of cysts that originated in the peritoneum of the rectouterine pouch and histopathologic diagnosis was confirmed as MBM of the pelvic peritoneum. We hope to alert gynaecologists of the diagnostic and therapeutic approaches to MBM which can be accomplished by laparoscopy.
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http://dx.doi.org/10.5468/OGS.2013.56.2.126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3784095PMC
March 2013

1p36.22 region containing PGD gene is frequently gained in human cervical cancer.

J Obstet Gynaecol Res 2014 Feb 11;40(2):545-53. Epub 2013 Oct 11.

Department of Obstetrics and Gynecology, Kangdong Sacred Heart Hospital, Hallym University, Seoul, Korea.

Aim: To identify commonly occurring DNA copy number alterations in Korean cervical cancers.

Methods: DNA copy number alteration was screened by whole-genome array comparative genomic hybridization (CGH) analysis. For the array CGH discovery, genomic DNA from five cervical cancers and 10 normal cervical tissues were examined. For the independent validation of the most significant chromosomal alteration (1p36.22, PGD gene), 40 formalin-fixed paraffin-embedded cervical tissue samples were collected; 10 of them were used for quantitative polymerase chain reaction and the other 30 samples were used for immunohistochemical analysis. Chromosomal segments differently distributed between cancers and normal controls were determined to be recurrently altered regions (RAR).

Results: A total of 13 RAR (11 RAR losses and two RAR gains) were defined in this study. Of the 13 cervical cancer-specific RAR, RAR gain in the 1p36.22 locus where the PGD gene is located was the most commonly detected in cancers (P = 0.004). In the quantitative polymerase chain reaction replication, copy number gain of the PGD gene was consistently identified in cervical cancers but not in the normal tissues (P = 0.02). In immunohistochemical analysis, PGD expression was significantly higher in cervical cancers than normal tissues (P = 0.02).

Conclusion: Our results will be helpful to understand cervical carcinogenesis, and the PGD gene can be a useful biomarker of cervical cancer.
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http://dx.doi.org/10.1111/jog.12193DOI Listing
February 2014

Human papillomavirus type 16 causes larger colposcopic lesions than other HPV types in patients with grade 3 cervical intraepithelial neoplasia.

J Low Genit Tract Dis 2013 Jan;17(1):1-5

Soonchunhyang University, Gyunggi-do, Korea.

Objective: Recent studies have shown that human papillomavirus (HPV) type 16 causes more definite visual abnormalities on cervigram than other HPV types and is thus easier to evaluate colposcopically. We examined factors, including HPV-16, related to colposcopic lesions in patients with grade 3 cervical intraepithelial neoplasia (CIN 3).

Methods: A retrospective chart review included 108 women with CIN 3 who underwent the loop electrosurgical excision procedure (LEEP). Lesions were assessed according to the number of cervical quadrant(s) involved by colposcopy, dichotomized as 2 or fewer or 3 or more quadrants involved. The Hybrid Capture 2 (HC2) test and HPV DNA chip assay (MyGene Co, Seoul, Korea) were used to detect HPV before punch biopsy or loop electrosurgical excision procedure. The type of HPV was dichotomized as HPV-16 or other (including negative cases). The HC2 viral load cutoff was 300 relative light units. Cytology was dichotomized as (1) low grade, less than, or equal to low-grade squamous lesions; or (2) high-grade, with high-grade squamous lesions or worse. Age and menopausal status were also assessed.

Results: The mean (SD) age of the 108 women was 41.9 (10.7) years (range = 22-76 y). Seventy-one (65.7%) had lesions involving 2 quadrants or fewer and 37 (34.3%) had lesions involving 3 quadrants or more. Multiple logistic regression revealed that larger lesions (≥3 quadrants involved) were significantly associated with HPV-16 (p = .032, odds ratio [OR] = 2.552, 95% confidence interval = 1.085-6.000) but not with age, menopausal status, cytologic grade, or HPV HC2 viral load.

Conclusions: Our data suggest that colposcopic lesions differ according to HPV type and that HPV-16 is associated with larger lesions, facilitating lesion detection by colposcopy.
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http://dx.doi.org/10.1097/LGT.0b013e31825afd5bDOI Listing
January 2013

Early human papillomavirus testing predicts residual/recurrent disease after LEEP.

J Gynecol Oncol 2012 Oct 19;23(4):217-25. Epub 2012 Sep 19.

Department of Obstetrics & Gynecology, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.

Objective: The purpose of this study was to determine the predictive factors for residual/recurrent disease and to analyze the timing for Pap smears and human papillomavirus (HPV) testing during follow-up after loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia (CIN) 2 or worse.

Methods: We retrospectively analyzed 183 patients (mean age, 39.3 years) with CIN 2/3 who were treated with LEEP. Post-LEEP follow-up was performed by Pap smear and HPV hybrid capture2 (HC2) testing. The definition of persistent/recurrent disease was biopsy-proven CIN 2 or worse.

Results: Among 183 patients, punch biopsies were CIN 2 in 31 (16.9%) and CIN 3 in 152 (83.1%). HPV HC2 tests before LEEP were positive in 170 (95.5%) of 178 patients. During follow-up, 12 patients (6.6%) had residual/recurrent CIN 2+. LEEP margin status was a significant predictive factor for persistent/recurrent disease. Other factors such as age, HPV HC2 viral load (≥100 relative light units), and HPV typing (type 16/18 vs. other types) did not predict recurrence. Early HPV HC2 testing at 3 months after LEEP detected all cases of residual/recurrent disease. The sensitivity and negative predictive value of the HPV HC2 test for residual/recurrent disease were both 100% at 3 and 6 months.

Conclusion: Margin involvement in conization specimens was a significant factor predicting residual/recurrent disease after LEEP. HPV test results at 3 and 6 months after treatment were comparable. Early 3-month follow-up testing after LEEP can offer timely information about residual/recurrent disease and alleviate patient anxiety early about treatment failure.
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http://dx.doi.org/10.3802/jgo.2012.23.4.217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3469856PMC
October 2012

Klotho inhibits the capacity of cell migration and invasion in cervical cancer.

Oncol Rep 2012 Sep 14;28(3):1022-8. Epub 2012 Jun 14.

Research Center for Women's Diseases and Department of Biological Sciences, Sookmyung Women's University, Seoul, Republic of Korea.

Aberrant activation of the Wnt/β-catenin signaling pathway is common in human cervical cancers. However, the mechanisms of Wnt activation in cervical cancer remain largely unknown. In the present study, we demonstrate that Klotho, a Wnt antagonist, is downregulated in invasive human cervical tumors and in a cell line we analyzed. Our data demonstrated that in vivo Klotho expression was not observed in invasive cervical carcinoma. In vitro restoration of Klotho expression in SiHa cells resulted in a decreased cell motility and invasiveness through upregulation of E-cadherin, downregulation of N-cadherin and reduced expression of MMP7 and -9. Ectopic expression of Klotho also reduced the expression of the epithelial-to-mesenchymal transition (EMT) transcription factors Slug and Twist. Furthermore, Klotho causes a significant inhibition of the Wnt/β-catenin pathway in cervical cancer cells, as supported by the expression of Wnt/β-catenin transcriptional target genes such as c-Myc and cyclin D1. Consequently, our findings demonstrate for the first time that Klotho regulates tumor invasion through the EMT process and provide novel mechanistic insights into the role of Klotho in cervical cancer progression and contribute to treatment for metastatic cervical cancer patients.
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http://dx.doi.org/10.3892/or.2012.1865DOI Listing
September 2012

Random biopsy after colposcopy-directed biopsy improves the diagnosis of cervical intraepithelial neoplasia grade 2 or worse.

J Low Genit Tract Dis 2010 Oct;14(4):346-51

Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, Soonchunhyang University Hospital, Bucheon-Si, Gyunggi-Do, Republic of Korea.

Objectives: To evaluate the usefulness of additional random biopsies in the diagnosis of cervical intraepithelial neoplasia grade 2 (CIN 2) or worse (CIN 2+) after colposcopy-directed biopsy.

Materials And Methods: A retrospective chart review was performed in 107 women with satisfactory colposcopy results after colposcopy-directed biopsy with random biopsy for abnormal cervical cytological evaluation at Soonchunhyang University Hospital between April 2008 and November 2009. Random biopsies were performed at the cervical squamocolumnar junction in lesion-free quadrants of the cervix. Loop electrosurgical excision procedure conizations were performed in 59 women. Age, referral cytology, lesion size, human papilloma virus (HPV) viral load, and HPV type were analyzed as possible indicators of lesion severity detected using random biopsy.

Results: The mean age was 39.3 years (range = 21-72 y), and 96 (89.7%) women were premenopausal. Sixty-three women had CIN 2+; of those, 8 (12.7%) were diagnosed using random biopsies: 6 had high-grade squamous intraepithelial lesions; 1 had low-grade squamous intraepithelial lesions; and 1 had atypical squamous cells of undetermined significance. Lesions diagnosed as CIN 2+ using random biopsies were significantly correlated with high-grade cytology (p <.001) and lesion size (p <.001) but not age (cutoff = 40 years), HPV viral load (cutoff = 300 relative light units; Hybrid Capture 2), or HPV genotype. Of 59 patients who underwent loop electrosurgical excision procedure conization, the disease severity of 9 (15.3%) cases was upgraded 1 or more grades, compared with the punch biopsy results.

Conclusions: The detection of CIN 2+, particularly high-grade cytological abnormalities and large lesion size, can be increased by additional random biopsies after satisfactory colposcopy. Loop electrosurgical excision procedure conization can detect lesions not detected by punch biopsy.
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http://dx.doi.org/10.1097/LGT.0b013e3181e9635bDOI Listing
October 2010

The anti-aging gene KLOTHO is a novel target for epigenetic silencing in human cervical carcinoma.

Mol Cancer 2010 May 18;9:109. Epub 2010 May 18.

Research Center for Women's Diseases and Division of Biological Science, Sookmyung Women's University, Seoul 140-742, Republic of Korea.

Background: Klotho was originally characterized as an anti-aging gene that predisposed Klotho-deficient mice to a premature aging-like syndrome. Recently, KLOTHO was reported to function as a secreted Wnt antagonist and as a tumor suppressor. Epigenetic gene silencing of secreted Wnt antagonists is considered a common event in a wide range of human malignancies. Abnormal activation of the canonical Wnt pathway due to epigenetic deregulation of Wnt antagonists is thought to play a crucial role in cervical tumorigenesis. In this study, we examined epigenetic silencing of KLOTHO in human cervical carcinoma.

Results: Loss of KLOTHO mRNA was observed in several cervical cancer cell lines and in invasive carcinoma samples, but not during the early, preinvasive phase of primary cervical tumorigenesis. KLOTHO mRNA was restored after treatment with either the DNA demethylating agent 2'-deoxy-5-azacytidine or histone deacetylase inhibitor trichostatin A. Methylation-specific PCR and bisulfite genomic sequencing analysis of the promoter region of KLOTHO revealed CpG hypermethylation in non-KLOTHO-expressing cervical cancer cell lines and in 41% (9/22) of invasive carcinoma cases. Histone deacetylation was also found to be the major epigenetic silencing mechanism for KLOTHO in the SiHa cell line. Ectopic expression of the secreted form of KLOTHO restored anti-Wnt signaling and anti-clonogenic activity in the CaSki cell line including decreased active beta-catenin levels, suppression of T-cell factor/beta-catenin target genes, such as c-MYC and CCND1, and inhibition of colony growth.

Conclusions: Epigenetic silencing of KLOTHO may occur during the late phase of cervical tumorigenesis, and consequent functional loss of KLOTHO as the secreted Wnt antagonist may contribute to aberrant activation of the canonical Wnt pathway in cervical carcinoma.
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http://dx.doi.org/10.1186/1476-4598-9-109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2885346PMC
May 2010

Angiomyofibroblastoma of the vulva: sonographic and computed tomographic findings with pathologic correlation.

J Ultrasound Med 2009 Oct;28(10):1417-20

Department of Radiology, Cheonan Hospital, Soonchunhyang University School of Medicine, Choongnam, Korea.

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http://dx.doi.org/10.7863/jum.2009.28.10.1417DOI Listing
October 2009

Factors associated with HPV persistence after conization in patients with negative margins.

J Gynecol Oncol 2009 Jun 29;20(2):91-5. Epub 2009 Jun 29.

Department of Obstetrics and Gynecology, College of Medicine, Soonchunhyang University, Bucheon, Korea.

Objective: The clearance rate of human papillomavirus (HPV) after conization is generally high, although some HPV infections persist. We investigated the factors that affect the clearance of HPV after conization in patients with negative margins.

Methods: We retrospectively analyzed 77 patients (mean age 39.9 years, range 25 to 51 years) with CIN 2/3 who underwent loop electrosurgical excision procedure (LEEP) conization with negative margins. All patients had a Pap smear and high-risk (HR) HPV testing using Hybrid Capture II system and HPV DNA chip before conization. We used>/=1 relative light units (RLUs) as the cutoff for persistence of HPV after conization.

Results: High-risk HPV was detected in 73 of 77 (94.8%) patients before conization. At the 6-months follow-up, the high-risk HPV was eliminated in 60 of 73 (82.2%) patients. The HPV persistence rate after conization was 17.8% (13/73). Univariate analysis showed that persistent HPV infection after conization with negative margins was more likely to occur when the pretreatment viral load was high (RLU/positive control >100 (p=0.027) and the HPV was type 16 (p=0.021). Logistic regression analysis showed that preoperative HPV type 16 infection was the only significant independent factor (p=0.021) for HPV persistence out of age, cytology, punch biopsy histology, HPV viral load, and conization histology.

Conclusion: Conization effectively removes HR-HPV infection. HPV type 16 infection before conization was significantly related to HR-HPV persistence after conization with negative margins. Therefore, patients with HPV 16 infection before conization need to be followed closely.
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http://dx.doi.org/10.3802/jgo.2009.20.2.91DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2705006PMC
June 2009
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