1.WWP2 ubiquitin ligase promotes colorectal cancer progression by targeting p53 for degradation:an experimental study
Seung-Jun LEE ; Han-Gil KIM ; Young-Tae JU ; Young-Sool HAH ; Jeongyun HWANG ; Jihun CHOI ; Jin-Kyu CHO ; Chi-Young JEONG ; Young-Joon LEE ; Ji-Ho PARK ; Ju-Yeon KIM ; Jae-Myung KIM ; Seung-Jin KWAG
Annals of Surgical Treatment and Research 2026;110(5):331-346
Purpose:
Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, necessitating the identification of novel therapeutic targets. The E3 ubiquitin ligase WW domain-containing E3 ubiquitin protein ligase 2 (WWP2) has been implicated in various cancers, yet its specific role and underlying molecular mechanisms in CRC are poorly understood. This study aimed to investigate the functional role of WWP2 in CRC progression and to elucidate its regulatory mechanisms.
Methods:
WWP2 expression was evaluated in CRC patient tissues and cell lines using immunohistochemistry, quantitative real-time polymerase chain reaction, and western blotting. The biological functions of WWP2 were assessed using in vitro assays for cell proliferation, migration, and invasion following adenovirus-mediated overexpression. The molecular mechanism was investigated by analyzing the protein expression levels of p53 and its downstream target, p21, via western blot. An in vivo xenograft mouse model was used to confirm the oncogenic role of WWP2.
Results:
WWP2 expression was significantly upregulated in CRC tissues. Overexpression of WWP2 promoted CRC cell proliferation, migration, and invasion. Mechanistically, increased WWP2 expression led to a marked reduction in the protein levels of the tumor suppressor p53. Consequently, the expression of the p53 downstream target, the cell cycle inhibitor p21, was also suppressed. In the xenograft model, WWP2 overexpression significantly enhanced tumor growth.
Conclusion
Our findings demonstrate that WWP2 functions as an oncogene in CRC. It promotes cancer progression by destabilizing the tumor suppressor p53 and downregulating p21. This study highlights the WWP2-p53-p21 axis as a potential novel therapeutic target for CRC.
2.Impact of smoking and age on long-term recurrence after laparoscopic primary closure for duodenal ulcer perforation: a 5-year observational study
Tae-Han KIM ; Sang-Ho JEONG ; Young-Joon LEE ; Dong-Hwan KIM ; Han-Gil KIM ; Jae-Myung KIM ; Jin-Kyu CHO ; Seung-Jin KWAG ; Ju-Yeon KIM ; Young-Tae JU ; Chi-Young JEONG ; Ji-Ho PARK
Annals of Surgical Treatment and Research 2025;109(2):98-104
Purpose:
This study investigates risk factors for recurrence in patients who underwent laparoscopic primary closure (PC) for pyloroduodenal ulcer perforation (PUP).
Methods:
We retrospectively analyzed data from patients who underwent laparoscopic PC with or without highly selective vagotomy (HSV) for PUP at a tertiary hospital from 2010 to 2019. Demographics, surgical outcomes, proton pump inhibitor (PPI) use, Helicobacter pylori status, and endoscopic findings were reviewed. Long-term (5 years) endoscopic and clinical outcomes regarding ulcer and perforation recurrence, were collected.
Results:
A total of 139 patients were included in the analysis. Of these, 109 (78.4%) were male, and 76 (54.7%) were current smokers. Ninety-five patients (68.3%) underwent PC only, while 44 (31.7%) received PC + HSV. During the follow-up period, ulcer recurrence was observed in 19 patients (13.7%) and perforation recurrence in 9 (6.5%). In Cox proportional analysis for ulcer recurrence, smoking (hazard ratio [HR], 6.476; 95% confidence interval [CI], 1.834–22.873; P = 0.004) and older age (HR, 1.049; 95% CI, 1.012–1.088; P = 0.009) were identified as significant factors. For peptic ulcer perforation recurrence, smoking (HR, 19.129; 95% CI, 2.048–178.702; P = 0.010) and older age (HR, 1.062; 95% CI, 1.009–1.118; P = 0.021) were significant. No significant associations were found between sex, duration of PPI therapy, H. pylori eradication success, or surgery type and the risk of either ulcer or perforation recurrence.
Conclusion
Smoking and age are important factors for recurrence following laparoscopic PC for PUP. These findings emphasize the need for smoking cessation and close postoperative monitoring.
3.MicroRNA-18b regulates cell cycle progression in papillary thyroid carcinoma by targeting CDK2: an in vitro experimental study
Ju-Yeon KIM ; Jae-Myung KIM ; Eun Jung JUNG ; Youngsim SON ; Seung-Jin KWAG ; Ji-Ho PARK ; Jin-Kyu CHO ; Han-Gil KIM ; Dong-Hwan KIM ; Sang-Ho JEONG ; Chi-Young JEONG ; Young-Tae JU ; Young-Joon LEE
Annals of Surgical Treatment and Research 2025;108(6):374-389
Purpose:
Papillary thyroid carcinoma (PTC) is the most prevalent endocrine malignancy, and the global incidence has been steadily increasing over the years. Although PTC generally exhibits favorable prognosis, a subset of patients experiences aggressive progression and increased mortality. Current prognostic approaches, reliant on clinic-pathological factors, have limitations, underscoring the need for innovative biomarkers. MicroRNAs (miRs) have emerged as promising candidates due to their roles in cellular processes and cancer progression. Among them, the present study investigated the role of miR-18b in PTC, exploring its potential as a prognostic biomarker.
Methods:
Utilizing PTC cell lines (TPC1, K1), we examined miR-18b expression and its regulatory effects. The present study used web-based tools to predict the target of miR-18b and to investigate the prognostic impact of miR-18b on thyroid cancer.
Results:
Through a series of cell proliferation, invasion assay, gap closure, and colony formation assays, we identified that miR-18b suppresses PTC aggressiveness. Dual-luciferase assays confirmed that miR-18b directly targeted the 3’-untranslated region of CDK2 and suppressed the expression of CDK2. In addition, miR-18b significantly attenuates the interaction between cyclin A or cyclin E with cyclin-dependent kinase 2 according to co-immunoprecipitation assay.Western blotting of cell cycle proteins and flow cytometry revealed miR-18b–induced cell cycle arrest and apoptosis.
Conclusion
Our findings underscore miR-18b’s potential as a biomarker for predicting the prognosis of PTC and suggest that it functions through direct regulation of CDK2, influencing cell cycle dynamics. This study not only enhances our understanding of miR-18b in thyroid cancer but also highlights its potential in refining prognostic evaluations and therapeutic strategies.
4.Experience of surgical treatment in a granular cell tumor in the qscending colon: a case report
In-Kyeong KIM ; Young-Tae JU ; Han-Gil KIM ; Jin-Kwon LEE ; Dong-Chul KIM ; Jae-Myung KIM ; Jin Kyu CHO ; Ji-Ho PARK ; Ju-Yeon KIM ; Chi-Young JEONG ; Soon-Chan HONG ; Seung-Jin KWAG
Annals of Coloproctology 2023;39(3):275-279
We report a case about successful surgical treatment of a granular cell tumor in the ascending colon. A 36-year-old man underwent screening colonoscopy. An endoscopic examination revealed a 10-mm yellowish and hemispheric mass in the ascending colon, and lower endoscopic ultrasonography revealed a hypoechoic-to-isoechoic mass invaded the submucosal layer. The mass was suspected to be a colonic carcinoid tumor. Based on the preoperative evaluation, endoscopic complete resection was considered difficult. Therefore, the lesion was removed via laparoscopic right hemicolectomy. Histological examination revealed that the tumor consisted of nests of polygonal cells with abundant granular eosinophilic cytoplasm. Immunohistochemical staining revealed diffuse positivity for S100 and CD68. Therefore, the tumor was diagnosed as a granular cell tumor. We suggest that surgical resection should be considered if it is located in the thin-walled ascending colon prone to perforation, difficult to rule out malignant tumor due to submucosal invasion, or to remove endoscopically.
5.The prognostic impact of body mass index in breast cancer according to tumor subtype
Jae-Myung KIM ; Ju-Yeon KIM ; Eun Jung JUNG ; Seung-Jin KWAG ; Ji-Ho PARK ; Jin-Kyu CHO ; Han-Gil KIM ; Chi-Young JEONG ; Young-Tae JU ; Young-Joon LEE
Korean Journal of Clinical Oncology 2023;19(2):52-59
Purpose:
Several studies demonstrated that obesity and underweight were negatively associated with outcomes of breast cancer. However, the results are still controversial, and the impact of body mass index (BMI) on distant metastasis-free survival (MFS), which might directly affect mortality, was less well evaluated. Our study aimed to verify the prognostic effect of BMI in breast cancer.
Methods:
A retrospective analysis of 504 patients with stage I-III breast cancer who underwent surgery from January 2005 to December 2013 was performed. The patients were divided into three groups according to preoperative BMI: underweight <18.5 kg/m2, normal weight 18.5–24.9 kg/m2, and overweight ≥25 kg/m2. The association between body weight status and breast cancer recurrence was analyzed. Subgroup analysis by tumor subtype according to receptor status was also performed.
Results:
The median follow-up period was 88 months. For disease recurrence, histologic grade and human epidermal growth factor receptor 2 (HER2)-positivity were independent prognostic factors in multivariate analysis. Stage, histologic grade, HER2-positivity, and BMI status were independent prognostic factors for distant metastasis. In survival analysis, overweight and underweight were significant predisposing factors for MFS, but not for disease-free survival (DFS). In the estrogen receptor (ER)-positive group, overweight and underweight patients had significantly worse DFS and MFS than normal weight patients. In the ER-negative or HER2-positive group, BMI status had no significant association with DFS and MFS.
Conclusion
The prognostic role of BMI on the survival outcomes of patients with breast cancer was different by tumor subtype. In ER-positive patients, overweight and underweight statuses had a negative prognostic effect on DFS and MFS, respectively.
6.Perioperative considerations for acute appendicitis in patients with COVID-19 infection: two case reports
In-Kyeong KIM ; Seung-jin KWAG ; Han-Gil KIM ; Young-Tae JU ; Seung-Jun LEE ; Tae-Jin PARK ; Sang-Ho JEONG ; Eun-Jung JUNG ; Jin-Kwon LEE
Annals of Coloproctology 2023;39(6):521-525
We report considerations related with surgery through 2 cases of acute apendicitis with COVID-19 infection. In November and December 2020, two patients infected with COVID-19 developed acute apendicitis and underwent emergency surgery. In case 1, an 84-year-old woman was asymptomatic and diagnosed with acute apendicitis on the 20th day of infection. She was discharged after surgery without complication. In contrast, case 2 was a 69-year-old male patient with pneumonia treated with antibiotics, steroids and remdesivir. After surgery, he was hospitalized for a long duration due to persistent pneumonia and wound complications. We should perform appendectomy in well-established negative pressure operating rooms, personal protective equipment, and protocols. Since the physical examination and blood tests were limited, image examination like computed tomography scan should be considered if acute apendicitis is suspected. If the patient has pneumonia before surgery, it can get worse after surgery, and complications such as wound infections can occur.
7.Exploring the role of copine 1 in human colorectal cancer:investigating its association with tumorigenesis and metastasis
Jin-Kwon LEE ; Seung-Jun LEE ; Young-Sool HAH ; Yeong-Ho JI ; Young-Tae JU ; Young-Joon LEE ; Chi-Young JEONG ; Ju-Yeon KIM ; Ji-Ho PARK ; Jae-Myung KIM ; Jin-Kyu CHO ; Han-Gil KIM ; Seung-Jin KWAG
Annals of Surgical Treatment and Research 2023;105(6):385-395
Purpose:
This study aimed to investigate the potential role of copine-1 (CPNE1), a calcium-dependent membrane-binding protein encoded by the CPNE1 gene, in colorectal cancer (CRC). Despite previous research on the involvement of copine family members in various solid tumors, the specific role of CPNE1 in CRC remains poorly understood.
Methods:
We conducted clinicopathological analysis and functional studies to explore the impact of CPNE1 in human CRC.We examined the expression levels of CPNE1 in CRC patients and correlated it with invasive depth, lymph node metastasis, distant metastasis, lymphatic invasion, and TNM stage. Additionally, we performed experiments to assess the functional consequences of CPNE1 knockdown in CRC cells, including proliferation, colony formation, migration, invasion, and the expression of key regulators involved in the cell cycle and epithelial-mesenchymal transition (EMT). Furthermore, we evaluated the effects of CPNE1 knockdown on tumor growth using a xenograft mouse model.
Results:
High expression of CPNE1 was significantly associated with advanced tumor features in CRC patients. CPNE1 knockdown in CRC cells led to impaired abilities in proliferation, colony formation, migration, and invasion. Furthermore, CPNE1 silencing resulted in the suppression of protein expression related to the cell cycle and EMT. In the xenograft mouse model, CPNE1 knockdown inhibited tumor growth.
Conclusion
CPNE1 plays a crucial role in promoting tumorigenesis and metastasis in human CRC. By regulating the cell cycle and EMT, CPNE1 influences critical cellular processes at the membrane-cytoplasm interface. These results provide valuable insights into the potential development of novel therapeutic strategies for CRC targeting CPNE1.
8.Ileocolonic intussusception caused by epithelioid leiomyosarcoma of the ileum: a report of case and review of the literature
Han-Gil KIM ; Jung Wook YANG ; Soon-Chan HONG ; Young-Tae JU ; Chi-Young JEONG ; Ju-Yeon KIM ; Ji-Ho PARK ; Jin-Kwon LEE ; Jae-Myung KIM ; Jin-Kyu CHO ; Seung-Jin KWAG
Annals of Coloproctology 2022;38(2):176-180
Small intestinal malignant tumor accounts for about 3% of all malignant tumors in the gastrointestinal tract, among which 13% are leiomyosarcoma (LMS). In addition, epithelioid LMS is of very rare occurrence. As small intestinal malignant tumors are initially asymptomatic and nonspecific, diagnosis is often delayed, and this can lead to large tumor at the time of detection and lead to intussusception. We observed ileocolonic intussusception in an 80-year-old male patient who was admitted to the hospital with a complaint of abdominal pain and palpable mass on right lower quadrant. The laparoscopic ileocecectomy was performed by the emergency operation because of obstruction. The pathologic examination revealed that the epithelioid LMS developed in the terminal ileum was the leading point of intussusception. To the best of our knowledge, laparoscopic surgery for ileocolonic intussusception with epithelioid LMS has not yet been reported.
9.Laparoscopic Local Resection through Subserosal Dissection with Endoscopic Air-Insufflation for Submucosal Tumors Located Near the Esophagogastric Junction
In-Kyeong KIM ; Ji-Ho PARK ; Young-Joon LEE ; Sang-Ho JEONG ; Tae Han KIM ; Dong-Hwan KIM ; Han-Gil KIM ; Jin-Kyu CHO ; Jae-Myung KIM ; Seung-Jin KWAG ; Ju-Yeon KIM ; Chi-Young JEONG ; Young-tae JU ; Eun-Jung JUNG ; Soon-Chan HONG
Journal of Minimally Invasive Surgery 2020;23(4):172-178
Purpose:
A novel resection method, namely, laparoscopic local resection through subserosal dissection with endoscopic air-insuff lation (LRSDEA) was used for submucosal tumors located near the esophagogastric junction (SMT-EGJ) to avoid major gastric resection.
Methods:
A total of 9 cases underwent LRSDEA. We sequentially performed: laparoscopic dissections around EGJ, subserosal dissections around SMTs using laparoscopic electrocautery and ultrasonic shears, and finally, enucleation of SMTs. During these procedures, intraoperative endoscopic tumor localization, as well as endoscopic air-insufflation allowed for safe resection. These procedures are shown in the supplementary video clip. The clinicopathological characteristics and surgical results were analyzed.
Results:
All laparoscopic procedures were successfully performed without requiring a major gastrectomy.The mean operation time was 126.1 minutes, and estimated blood loss was 12.0 ml. There were no postoperative complications. Pathological diagnoses were 6 leiomyomas, 2 gastrointestinal stromal tumors, and 1 gastric duplication.
Conclusion
LRSDEA is an effective and safe treatment option for SMT-EGJ, as major resection of the stomach is avoided.
10.Safety of subtotal or total colectomy with primary anastomosis compared to Hartmann procedure for left-sided colon cancer obstruction or perforation
Eun Do KIM ; Jin Kwon LEE ; Jin Kyu CHO ; Jae Myung KIM ; Ji Ho PARK ; Ju Yeon KIM ; Sang Ho JEONG ; Young Tae JU ; Chi Young JEONG ; Eun Jung JUNG ; Young Joon LEE ; Soon Chan HONG ; Seung Jin KWAG
Korean Journal of Clinical Oncology 2019;15(2):106-111
PURPOSE: Whether subtotal or total colectomy with primary anastomosis (PA) is safer than Hartmann procedure (HP) for left-sided colon cancer obstruction or perforation remains controversial. The purpose of this study was to compare postoperative morbidity, mortality, and defecation frequency between PA and HP for left-sided colon cancer obstruction or perforation.METHODS: This retrospective study enrolled 54 patients from January 2014 to February 2018 who underwent emergency surgery due to left-sided colon cancer obstruction or perforation.RESULTS: PA was carried out in 20 patients while HP was performed for 34 patients. Thirty-day mortality did not show significant difference between the two groups (15.0% vs. 14.7%, P=1.000). No anastomotic leakage occurred in PA group while three (8.8%) cases of stump leakage occurred in HP group. Stoma repair was performed for 13 cases (44.8%) and stoma reformation was performed for one case in HP group (7.7%). Stoma related complications occurred in five cases (17.24%). For patients after stoma repair, defecation frequency at 3 months after operation was 2.91±2.88 times per day in PA group and 2.86±2.63 times per day in HP group. At 1 year after operation, defecation frequency was changed to 1.40±1.12 times per day in PA group and 1.17±0.39 times per day in HP group.CONCLUSION: Primary ileosigmoid or ileorectal anastomosis for left-sided colon cancer obstruction or perforation is safe, and shows similar outcome of defecation frequency compared to HP.
Anastomotic Leak
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Colectomy
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Colon
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Colonic Neoplasms
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Defecation
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Emergencies
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Humans
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Mortality
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Retrospective Studies

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