1.Chemosensitivity to doxorubicin in primary cells derived from tumor of FVB/N‑Trp53tm1Hw1 with TALEN‑mediated Trp53 mutant gene
Woobin YUN ; Ji Eun KIM ; You Jeong JIN ; Yu Jeong ROH ; Hee Jin SONG ; Ayun SEOL ; Tae Ryeol KIM ; Kyeong Seon MIN ; Eun Seo PARK ; Gi Ho PARK ; Hyun Gu KANG ; Yeon Shik CHOI ; Dae Youn HWANG
Laboratory Animal Research 2023;39(4):287-297
Background:
To evaluate the chemosensitivity to doxorubicin (DOX) in two primary cells derived from a tumor of FVB/N-Trp53tm1Hw1 knockout (KO) mice with TALEN-mediated Trp53 mutant gene, we evaluated the cell survivability, cell cycle distribution, apoptotic cell numbers and apoptotic protein expression in solid tumor cells and ascetic tumor cells treated with DOX.
Results:
The primary tumor cells showed a significant (P < 0.05) defect for UV-induced upregulation of the Trp53 pro-tein, and consisted of different ratios of leukocytes, fibroblasts, epithelial cells and mesenchymal cells. The IC50 level to DOX was lower in both primary cells (IC50 = 0.12 μM and 0.20 μM) as compared to the CT26 cells (IC50 = 0.32 μM), although the solid tumor was more sensitive. Also, the number of cells arrested at the G0/G1 stage was significantly decreased (24.7–23.1% in primary tumor cells treated with DOX, P < 0.05) while arrest at the G2 stage was enhanced to 296.8–254.3% in DOX-treated primary tumor cells compared with DOX-treated CT26 cells. Furthermore, apoptotic cells of early and late stage were greatly increased in the two primary cell-lines treated with DOX when compared to same conditions for CT26 cells. However, the Bax/Bcl-2 expression level was maintained constant in the primary tumor and CT26 cells.
Conclusions
To the best of our knowledge, these results are the first to successfully detect an alteration in chemosensitivity to DOX in solid tumor cells and ascetic tumor cells derived from tumor of FVB/N-Trp53tm1Hw1 mice TALENmediated Trp53 mutant gene.
2.Outcomes and prognostic factors of surgically treated extramammary Paget’s disease of the vulva
Angela CHO ; Dae-Yeon KIM ; Dae-Shik SUH ; Jong-Hyeok KIM ; Yong-Man KIM ; Young-Tak KIM ; Jeong-Yeol PARK
Journal of Gynecologic Oncology 2023;34(6):e76-
Objective:
Extramammary Paget’s disease (EMPD) of the vulva is a rare disease which predominantly presents in postmenopausal Caucasian women. As yet, no studies on Asian female patients with EMPD have been performed. This study aimed to identify the clinical features of patients with vulvar EMPD in Korea, and to evaluate the risk factors of recurrence and postoperative complications in surgically treated EMPD.
Methods:
We retrospectively reviewed 47 patients with vulvar EMPD who underwent wide local excision or radical vulvectomy. The clinical data and surgical and oncological outcomes following surgery were extracted from medical records and analyzed. Univariate and multivariate analyses for predicting recurrence and postoperative complications were performed.
Results:
21.3% of patients had complications after surgery, and wound dehiscence was the most common. 14.9% of patients experienced recurrence, and the median interval to recurrence from initial treatment was 69 (range 33–169) months. Vulvar lesions larger than 40 mm was the independent risk factor of postoperative complications (odds ratio [OR]=7.259; 95% confidence interval [CI]=1.545–34.100; p=0.012). Surgical margin status was not associated with recurrence in surgically treated vulvar EMPD patients (OR=0.83; 95% CI=0.16–4.19; p=1.000).
Conclusion
Positive surgical margin is a frequent finding in the patients with vulvar EMPD, but disease recurrence is not related with surgical margin status. Since EMPD is a slow growing tumor, a surveillance period longer than 5 years is required.
3.Ventricular late potentials measured by signal‑averaged electrocardiogram in young professional soccer players
Jung Myung LEE ; Hyemoon CHUNG ; Hyung‑Oh KIM ; Jong‑Shin WOO ; Soo Joong KIM ; Weon KIM ; Woo Shik KIM ; Jin‑Bae KIM
International Journal of Arrhythmia 2021;22(1):3-
Background and objectives:
Athlete’s heart is characterized by structural cardiac changes, including enlargement and hypertrophy. However, exercise-induced cardiac electrical remodeling is not well known in Asian athletes. We sought to evaluate the association between vigorous exercise and the development of abnormal late potential on signal-averaged electrocardiogram (SAECG).Method: We analyzed 48 Korean professional soccer players and 71 healthy sedentary controls who underwent SAECG and transthoracic echocardiography at Kyung Hee University Hospital. An SAECG was considered abnormal (positive for ventricular late potential) when any one of the three following criteria was met: filtered QRS dura‑ tion > 114 ms, root-mean-square voltage in the terminal 40 ms < 20 uV, or a voltage < 40 uV for more than 38 ms.
Results:
Fragmented QRS was more commonly found in athletes (1.4% vs. 10.4%). Athletes demonstrated signifi‑ cantly higher proportion of filtered QRS duration > 114 ms (7.0% vs. 22.9%, P = 0.013) and lower terminal QRS rootmean-square voltage < 20 uV (5.6% vs. 20.8%, P = 0.012). Ventricular late potential on SAECG was significantly more frequent in athletes (15.5% vs. 35.4%, P = 0.012). Regarding echocardiographic parameters, the athletes had larger cardiac chamber size; however, these differences became non-significant after adjustment for body surface area, except left ventricular mass index (65.7 ± 12.7 g/m2 vs. 84.7 ± 17.7 g/m2 , P < 0.001).
Conclusion
Abnormal SAECG findings were significantly more common in athletes than in controls. Further study is needed to determine the clinical impact of these abnormal SAECGs in athletes and cardiac outcomes in the long term.
4.Comparison of Long-Term Angiographic Results of Wide-Necked Intracranial Aneurysms : Endovascular Treatment with Single-Microcatheter Coiling, Double-Microcatheter Coiling, and Stent-Assisted Coiling
Hyun Sik KIM ; Byung Moon CHO ; Chan Jong YOO ; Dae Han CHOI ; Dong Keun HYUN ; Yu Shik SHIM ; Joon Ho SONG ; Jae Keun OH ; Jun Hyong AHN ; Ji Hee KIM ; In Bok CHANG
Journal of Korean Neurosurgical Society 2021;64(5):751-762
Objective:
: Endovascular treatment of intracranial aneurysms is challenging in case of wide-necked aneurysms because coils are prone to herniate into the parent artery, causing thromboembolic events or vessel occlusion. This study aims to compare long-term angiographic results of wide-necked aneurysms treated by stent-assisted, double-microcatheter, or single-microcatheter groups.
Methods:
: Between January 2003 and October 2016, 108 aneurysms that were treated with endovascular coil embolization with a neck size wider than 4 mm and a follow-up period of more than 3 years were selected. We performed coil embolization with singlemicrocatheter, double-microcatheter, and stent-assisted techniques. Angiographic results were evaluated using the Raymond-Roy occlusion classification (RROC). All medical and angiographic records were reviewed retrospectively.
Results:
: Clinical and angiographic analyses were conducted in 108 wide-necked aneurysms. The immediate post-procedural results revealed RROC class I (complete occlusion) in 66 cases (61.1%), class II (residual neck) in 36 cases (33.3%), and class III (residual sac) in six cases (5.6%). The final follow-up results revealed class I in 48 cases (44.4%), class II in 49 cases (45.4%), and class III in 11 cases (10.2%). Of a total of 45 (41.6%) radiologic recurrences, there were 21 cases (19.4%) of major recurrence that required additional treatment, and 24 cases (22.2%) of minor recurrence. The final follow-up angiographic results showed statistically significant differences between the stent-assisted group and the others (p<0.01).
Conclusion
: Long-term follow-up angiography demonstrated that the stent-assisted technique had a better complete occlusion rate than the other two techniques.
5.Comparison of response to LPS-induced sepsis in three DBA/2 stocks derived from different sources
Ji Won PARK ; Su Jin LEE ; Ji Eun KIM ; Mi Ju KANG ; Su Ji BAE ; Yun Ju CHOI ; Jeong Eun GONG ; Kil Soo KIM ; Young-Suk JUNG ; Joon-Yong CHO ; Yeon Shik CHOI ; Dae Youn HWANG ; Hyun Keun SONG
Laboratory Animal Research 2021;37(1):44-52
Sepsis, one of the most fatal diseases in the world, is known to culminate in multiple organ failure due to an uncontrolled inflammatory response. Hence, the use of animal models in sepsis research is very important to study complex immune responses. The current study was undertaken to compare commercial stocks with KFDA stocks of DBA/2 mice as an animal model for sepsis study. To compare responses of DBA/2 mice to lipopolysaccharides (LPS)-induced sepsis, we measured altered characteristics of various factors associated with sepsis, including survival curves, organ failure and inflammatory response, in DBA/2Korl stock and two commercial stocks (DBA/2A and DBA/ 2B). Survival rates after LPS exposure were similar for DBA/2Korl and DBA/2B; however, for times over 20 h, survival rates were reduced and concentration dependent in DBA/2A. In order to evaluate multiple organ failure caused by sepsis, H&E stains were evaluated for liver and spleen tissues obtained in the early (2 h) and later (20 h) stages after exposure to LPS; no significant differences were observed between the three stocks. mRNA and protein levels of proinflammatory cytokines were assessed for evaluating inflammatory reactions, and were found to increase in a dose-dependent manner in most DBA/2 mice after LPS treatment. However, no changes were observed in the mRNA levels of proinflammatory cytokines at 20 h after LPS exposure in the DBA/2A stock. The induction of inflammation-mediated factors by LPS exposure did not induce alterations in the mRNA levels of COX-2 and iNOS in all three DBA/2 stocks. Our results indicate that response of DBA/2Korl to LPS-induced sepsis is similar to the two commercial DBA/2 stocks, thus representing its potential as a useful biological resource established in Korea.
6.Comparison of response to LPS-induced sepsis in three DBA/2 stocks derived from different sources
Ji Won PARK ; Su Jin LEE ; Ji Eun KIM ; Mi Ju KANG ; Su Ji BAE ; Yun Ju CHOI ; Jeong Eun GONG ; Kil Soo KIM ; Young-Suk JUNG ; Joon-Yong CHO ; Yeon Shik CHOI ; Dae Youn HWANG ; Hyun Keun SONG
Laboratory Animal Research 2021;37(1):44-52
Sepsis, one of the most fatal diseases in the world, is known to culminate in multiple organ failure due to an uncontrolled inflammatory response. Hence, the use of animal models in sepsis research is very important to study complex immune responses. The current study was undertaken to compare commercial stocks with KFDA stocks of DBA/2 mice as an animal model for sepsis study. To compare responses of DBA/2 mice to lipopolysaccharides (LPS)-induced sepsis, we measured altered characteristics of various factors associated with sepsis, including survival curves, organ failure and inflammatory response, in DBA/2Korl stock and two commercial stocks (DBA/2A and DBA/ 2B). Survival rates after LPS exposure were similar for DBA/2Korl and DBA/2B; however, for times over 20 h, survival rates were reduced and concentration dependent in DBA/2A. In order to evaluate multiple organ failure caused by sepsis, H&E stains were evaluated for liver and spleen tissues obtained in the early (2 h) and later (20 h) stages after exposure to LPS; no significant differences were observed between the three stocks. mRNA and protein levels of proinflammatory cytokines were assessed for evaluating inflammatory reactions, and were found to increase in a dose-dependent manner in most DBA/2 mice after LPS treatment. However, no changes were observed in the mRNA levels of proinflammatory cytokines at 20 h after LPS exposure in the DBA/2A stock. The induction of inflammation-mediated factors by LPS exposure did not induce alterations in the mRNA levels of COX-2 and iNOS in all three DBA/2 stocks. Our results indicate that response of DBA/2Korl to LPS-induced sepsis is similar to the two commercial DBA/2 stocks, thus representing its potential as a useful biological resource established in Korea.
7.Ventricular late potentials measured by signal‑averaged electrocardiogram in young professional soccer players
Jung Myung LEE ; Hyemoon CHUNG ; Hyung‑Oh KIM ; Jong‑Shin WOO ; Soo Joong KIM ; Weon KIM ; Woo Shik KIM ; Jin‑Bae KIM
International Journal of Arrhythmia 2021;22(1):3-
Background and objectives:
Athlete’s heart is characterized by structural cardiac changes, including enlargement and hypertrophy. However, exercise-induced cardiac electrical remodeling is not well known in Asian athletes. We sought to evaluate the association between vigorous exercise and the development of abnormal late potential on signal-averaged electrocardiogram (SAECG).Method: We analyzed 48 Korean professional soccer players and 71 healthy sedentary controls who underwent SAECG and transthoracic echocardiography at Kyung Hee University Hospital. An SAECG was considered abnormal (positive for ventricular late potential) when any one of the three following criteria was met: filtered QRS dura‑ tion > 114 ms, root-mean-square voltage in the terminal 40 ms < 20 uV, or a voltage < 40 uV for more than 38 ms.
Results:
Fragmented QRS was more commonly found in athletes (1.4% vs. 10.4%). Athletes demonstrated signifi‑ cantly higher proportion of filtered QRS duration > 114 ms (7.0% vs. 22.9%, P = 0.013) and lower terminal QRS rootmean-square voltage < 20 uV (5.6% vs. 20.8%, P = 0.012). Ventricular late potential on SAECG was significantly more frequent in athletes (15.5% vs. 35.4%, P = 0.012). Regarding echocardiographic parameters, the athletes had larger cardiac chamber size; however, these differences became non-significant after adjustment for body surface area, except left ventricular mass index (65.7 ± 12.7 g/m2 vs. 84.7 ± 17.7 g/m2 , P < 0.001).
Conclusion
Abnormal SAECG findings were significantly more common in athletes than in controls. Further study is needed to determine the clinical impact of these abnormal SAECGs in athletes and cardiac outcomes in the long term.
8.Comparison of Long-Term Angiographic Results of Wide-Necked Intracranial Aneurysms : Endovascular Treatment with Single-Microcatheter Coiling, Double-Microcatheter Coiling, and Stent-Assisted Coiling
Hyun Sik KIM ; Byung Moon CHO ; Chan Jong YOO ; Dae Han CHOI ; Dong Keun HYUN ; Yu Shik SHIM ; Joon Ho SONG ; Jae Keun OH ; Jun Hyong AHN ; Ji Hee KIM ; In Bok CHANG
Journal of Korean Neurosurgical Society 2021;64(5):751-762
Objective:
: Endovascular treatment of intracranial aneurysms is challenging in case of wide-necked aneurysms because coils are prone to herniate into the parent artery, causing thromboembolic events or vessel occlusion. This study aims to compare long-term angiographic results of wide-necked aneurysms treated by stent-assisted, double-microcatheter, or single-microcatheter groups.
Methods:
: Between January 2003 and October 2016, 108 aneurysms that were treated with endovascular coil embolization with a neck size wider than 4 mm and a follow-up period of more than 3 years were selected. We performed coil embolization with singlemicrocatheter, double-microcatheter, and stent-assisted techniques. Angiographic results were evaluated using the Raymond-Roy occlusion classification (RROC). All medical and angiographic records were reviewed retrospectively.
Results:
: Clinical and angiographic analyses were conducted in 108 wide-necked aneurysms. The immediate post-procedural results revealed RROC class I (complete occlusion) in 66 cases (61.1%), class II (residual neck) in 36 cases (33.3%), and class III (residual sac) in six cases (5.6%). The final follow-up results revealed class I in 48 cases (44.4%), class II in 49 cases (45.4%), and class III in 11 cases (10.2%). Of a total of 45 (41.6%) radiologic recurrences, there were 21 cases (19.4%) of major recurrence that required additional treatment, and 24 cases (22.2%) of minor recurrence. The final follow-up angiographic results showed statistically significant differences between the stent-assisted group and the others (p<0.01).
Conclusion
: Long-term follow-up angiography demonstrated that the stent-assisted technique had a better complete occlusion rate than the other two techniques.
9.Robot-Assisted Laparoscopic Myomectomy versus Abdominal Myomectomy for Large Myomas Sized over 10 cm or Weighing 250 g
Sa Ra LEE ; Eun Sil LEE ; Young-Jae LEE ; Shin-Wha LEE ; Jeong Yeol PARK ; Dae-Yeon KIM ; Sung Hoon KIM ; Yong-Man KIM ; Dae-Shik SUH ; Young-Tak KIM
Yonsei Medical Journal 2020;61(12):1054-1059
Purpose:
Here, we compared the operative and perioperative outcomes between robot-assisted laparoscopic myomectomy (RALM) and abdominal myomectomy (AM) in patients with large (>10 cm) or heavy myomas (>250 g).
Materials and Methods:
We included 278 patients who underwent multi-port RALM (n=126) or AM (n=151) for large or heavy myomas in a tertiary care hospital between April 2019 and June 2020. The t-test, chi-square, Bonferroni’s test, and multiple linear regression were used.
Results:
No differences were observed in age, body mass index, parity, or history of pelvic surgery between the two groups. Myoma diameters were not different (10.8±2.52 cm vs. 11.2±3.0 cm, p=0.233), but myomas were lighter in the RALM group than in the AM group (444.6±283.14 g vs. 604.68±368.35 g, respectively, p=0.001). The RALM group had a higher proportion of subserosal myomas, fewer myomas, fewer large myomas over >3 cm, lighter myomas, and longer total operating time. However, the RALM group also had shorter hospital stay and fewer short-term complications. Estimated blood loss (EBL) was not different between the two groups. The number of removed myomas was the most significant factor (coefficient=10.89, p<0.0001) affecting the EBL.
Conclusion
RALM is a feasible myomectomy technique even for large or heavy myomas. RALM patients tend to have shorter hospital stays and fewer postoperative fevers within 48 hours. However, RALM has longer total operating time.
10.Feasibility and safety of fertilitysparing surgery in epithelial ovarian cancer with dense adhesion: a longterm result from a single institution
Min-Hyun BAEK ; Jeong-Yeol PARK ; Dae-Yeon KIM ; Dae-Shik SUH ; Jong-Hyeok KIM ; Yong-Man KIM ; Young-Tak KIM
Journal of Gynecologic Oncology 2020;31(6):e85-
Objective:
We investigated the feasibility and safety of fertility-sparing surgery (FSS) in patients with epithelial ovarian cancer (EOC) with dense adhesions.
Methods:
Patients were divided into cases with and without dense adhesions in this retrospective study.
Results:
Of the 95 eligible patients, 29 patients had dense adhesions. Mean age, proportion of staging procedure, distribution of histologic type, and co-presence of endometriosis were different (p=0.003, 0.033, 0.011, and 0.011, respectively). The median follow-up period was 57.8 (0.4–230.0) months. There were no differences in the rates of recurrence (21.2% vs.20.7%, p=1.000) or death (16.7% vs. 6.9%, p=0.332) between the 2 groups. There was no difference in the pattern of recurrence or in disease-free survival (DFS) and overall survival (OS) between the 2 groups. In multivariate analysis, pretreatment cancer antigen-125 >35 U/mL and International Federation of Gynecology and Obstetrics stage IC were significant factors of worse DFS and OS, while dense adhesion was not a prognostic factor for both DFS (hazard ratio [HR]=0.9; 95% confidence interval [CI]=0.3–2.7; p=0.792) and OS (HR=0.2; 95% CI=0.1–1.8; p=0.142), nor were age, proportion of staging procedure, histologic type, and co-presence of endometriosis. Moreover, the distribution of those 2 significant prognostic factors was not different between the 2 groups. Dense adhesions were subgrouped into nontumor and tumor associated dense adhesions for further analysis and the results were same.
Conclusion
FSS is feasible and safe in EOC, regardless of the presence of dense adhesions.

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