1.PDK4 expression and tumor aggressiveness in prostate cancer
Eun Hye LEE ; Yun-Sok HA ; Bo Hyun YOON ; Minji JEON ; Dong Jin PARK ; Jiyeon KIM ; Jun-Koo KANG ; Jae-Wook CHUNG ; Bum Soo KIM ; Seock Hwan CHOI ; Hyun Tae KIM ; Tae-Hwan KIM ; Eun Sang YOO ; Tae Gyun KWON
Investigative and Clinical Urology 2025;66(3):227-235
Purpose:
Prostate cancer ranks as the second most common cancer in men globally, representing a significant cause of cancer-related mortality. Metastasis, the spread of cancer cells from the primary site to distant organs, remains a major challenge in managing prostate cancer. Pyruvate dehydrogenase kinase 4 (PDK4) is implicated in the regulation of aerobic glycolysis, emerging as a potential player in various cancers. However, its role in prostate cancer remains unclear. This study aims to analyze PDK4 expression in prostate cancer cells and human samples, and to explore the gene's clinical significance.
Materials and Methods:
PDK4 expression was detected in cell lines and human tissue samples. Migration ability was analyzed using Matrigel-coated invasion chambers. Human samples were obtained from the Kyungpook National University Chilgok Hospital.
Results:
PDK4 expression was elevated in prostate cancer cell lines compared to normal prostate cells, with particularly high levels in DU145 and LnCap cell lines. PDK4 knockdown in these cell lines suppressed their invasion ability, indicating a potential role of PDK4 in prostate cancer metastasis. Furthermore, our results revealed alterations in epithelial-mesenchymal transition markers and downstream signaling molecules following PDK4 suppression, suggesting its involvement in the modulation of invasion-related pathways. Furthermore, PDK4 expression was increased in prostate cancer tissues, especially in castration-resistant prostate cancer, compared to normal prostate tissues, with PSA and PDK4 expression showing a significantly positive correlation.
Conclusions
PDK4 expression in prostate cancer is associated with tumor invasion and castration status. Further validation is needed to demonstrate its effectiveness as a therapeutic target.
2.Evaluation of the Efficacy and Safety of DW1903 in Patients with Gastritis: A Randomized, Double-Blind, Noninferiority, Multicenter, Phase 3 study
Jie-Hyun KIM ; Hwoon-Yong JUNG ; In Kyung YOO ; Seon-Young PARK ; Jae Gyu KIM ; Jae Kyu SUNG ; Jin Seok JANG ; Gab Jin CHEON ; Kyoung Oh KIM ; Tae Oh KIM ; Soo Teik LEE ; Kwang Bum CHO ; Hoon Jai CHUN ; Jong-Jae PARK ; Moo In PARK ; Jae-Young JANG ; Seong Woo JEON ; Jin Woong CHO ; Dae Hwan KANG ; Gwang Ha KIM ; Jae J. KIM ; Sang Gyun KIM ; Nayoung KIM ; Yong Chan LEE ; Su Jin HONG ; Hyun-Soo KIM ; Sora LEE ; Sang Woo LEE
Gut and Liver 2024;18(1):70-76
Background/Aims:
H2 receptor antagonists (H2RA) have been used to treat gastritis by inhibiting gastric acid. Proton pump inhibitors (PPIs) are more potent acid suppressants than H2RA.However, the efficacy and safety of low-dose PPI for treating gastritis remain unclear. The aim was to investigate the efficacy and safety of low-dose PPI for treating gastritis.
Methods:
A double-blind, noninferiority, multicenter, phase 3 clinical trial randomly assigned 476 patients with endoscopic erosive gastritis to a group using esomeprazole 10 mg (DW1903) daily and a group using famotidine 20 mg (DW1903R1) daily for 2 weeks. The full-analysis set included 319 patients (DW1903, n=159; DW1903R1, n=160) and the per-protocol set included 298 patients (DW1903, n=147; DW1903R1, n=151). The primary endpoint (erosion improvement rate) and secondary endpoint (erosion and edema cure rates, improvement rates of hemorrhage, erythema, and symptoms) were assessed after the treatment. Adverse events were compared.
Results:
According to the full-analysis set, the erosion improvement rates in the DW1903 and DW1903R1 groups were 59.8% and 58.8%, respectively. According to the per-protocol analysis, the erosion improvement rates in the DW1903 and DW1903R1 groups were 61.9% and 59.6%, respectively. Secondary endpoints were not significantly different between two groups except that the hemorrhagic improvement rate was higher in DW1903 with statistical tendency. The number of adverse events were not statistically different.
Conclusions
DW1903 of a low-dose PPI was not inferior to DW1903R1 of H2RA. Thus, lowdose PPI can be a novel option for treating gastritis (ClinicalTrials.gov Identifier: NCT05163756).
3.A Modified eCura System to Stratify the Risk of Lymph Node Metastasis in Undifferentiated-Type Early Gastric Cancer After Endoscopic Resection
Hyo-Joon YANG ; Hyuk LEE ; Tae Jun KIM ; Da Hyun JUNG ; Kee Don CHOI ; Ji Yong AHN ; Wan Sik LEE ; Seong Woo JEON ; Jie-Hyun KIM ; Gwang Ha KIM ; Jae Myung PARK ; Sang Gyun KIM ; Woon Geon SHIN ; Young-Il KIM ; Il Ju CHOI
Journal of Gastric Cancer 2024;24(2):172-184
Purpose:
The original eCura system was designed to stratify the risk of lymph node metastasis (LNM) after endoscopic resection (ER) in patients with early gastric cancer (EGC).We assessed the effectiveness of a modified eCura system for reflecting the characteristics of undifferentiated-type (UD)-EGC.
Materials and Methods:
Six hundred thirty-four patients who underwent non-curative ER for UD-EGC and received either additional surgery (radical surgery group; n=270) or no further treatment (no additional treatment group; n=364) from 18 institutions between 2005 and 2015 were retrospectively included in this study. The eCuraU system assigned 1 point each for tumors >20 mm in size, ulceration, positive vertical margin, and submucosal invasion <500 µm; 2 points for submucosal invasion ≥500 µm; and 3 points for lymphovascular invasion.
Results:
LNM rates in the radical surgery group were 1.1%, 5.4%, and 13.3% for the low-(0–1 point), intermediate- (2–3 points), and high-risk (4–8 points), respectively (P-fortrend<0.001). The eCuraU system showed a significantly higher probability of identifying patients with LNM as high-risk than the eCura system (66.7% vs. 22.2%; McNemar P<0.001).In the no additional treatment group, overall survival (93.4%, 87.2%, and 67.6% at 5 years) and cancer-specific survival (99.6%, 98.9%, and 92.9% at 5 years) differed significantly among the low-, intermediate-, and high-risk categories, respectively (both P<0.001). In the high-risk category, surgery outperformed no treatment in terms of overall mortality (hazard ratio, 3.26; P=0.015).
Conclusions
The eCuraU system stratified the risk of LNM in patients with UD-EGC after ER. It is strongly recommended that high-risk patients undergo additional surgery.
4.Transradial Versus Transfemoral Access for Bifurcation Percutaneous Coronary Intervention Using SecondGeneration Drug-Eluting Stent
Jung-Hee LEE ; Young Jin YOUN ; Ho Sung JEON ; Jun-Won LEE ; Sung Gyun AHN ; Junghan YOON ; Hyeon-Cheol GWON ; Young Bin SONG ; Ki Hong CHOI ; Hyo-Soo KIM ; Woo Jung CHUN ; Seung-Ho HUR ; Chang-Wook NAM ; Yun-Kyeong CHO ; Seung Hwan HAN ; Seung-Woon RHA ; In-Ho CHAE ; Jin-Ok JEONG ; Jung Ho HEO ; Do-Sun LIM ; Jong-Seon PARK ; Myeong-Ki HONG ; Joon-Hyung DOH ; Kwang Soo CHA ; Doo-Il KIM ; Sang Yeub LEE ; Kiyuk CHANG ; Byung-Hee HWANG ; So-Yeon CHOI ; Myung Ho JEONG ; Hyun-Jong LEE
Journal of Korean Medical Science 2024;39(10):e111-
Background:
The benefits of transradial access (TRA) over transfemoral access (TFA) for bifurcation percutaneous coronary intervention (PCI) are uncertain because of the limited availability of device selection. This study aimed to compare the procedural differences and the in-hospital and long-term outcomes of TRA and TFA for bifurcation PCI using secondgeneration drug-eluting stents (DESs).
Methods:
Based on data from the Coronary Bifurcation Stenting Registry III, a retrospective registry of 2,648 patients undergoing bifurcation PCI with second-generation DES from 21 centers in South Korea, patients were categorized into the TRA group (n = 1,507) or the TFA group (n = 1,141). After propensity score matching (PSM), procedural differences, in-hospital outcomes, and device-oriented composite outcomes (DOCOs; a composite of cardiac death, target vessel-related myocardial infarction, and target lesion revascularization) were compared between the two groups (772 matched patients each group).
Results:
Despite well-balanced baseline clinical and lesion characteristics after PSM, the use of the two-stent strategy (14.2% vs. 23.7%, P = 0.001) and the incidence of in-hospital adverse outcomes, primarily driven by access site complications (2.2% vs. 4.4%, P = 0.015), were significantly lower in the TRA group than in the TFA group. At the 5-year follow-up, the incidence of DOCOs was similar between the groups (6.3% vs. 7.1%, P = 0.639).
Conclusion
The findings suggested that TRA may be safer than TFA for bifurcation PCI using second-generation DESs. Despite differences in treatment strategy, TRA was associated with similar long-term clinical outcomes as those of TFA. Therefore, TRA might be the preferred access for bifurcation PCI using second-generation DES.
5.Hypofractionated radiation therapy combined with androgen deprivation therapy for clinically node-positive prostate cancer
Tae Hoon LEE ; Hongryull PYO ; Gyu Sang YOO ; Seong Soo JEON ; Seong Il SEO ; Byong Chang JEONG ; Hwang Gyun JEON ; Hyun Hwan SUNG ; Minyong KANG ; Wan SONG ; Jae Hoon CHUNG ; Bong Kyung BAE ; Won PARK
Radiation Oncology Journal 2024;42(2):139-147
Purpose:
This study aimed to analyze the treatment outcomes of combined definitive radiation therapy (RT) and androgen deprivation therapy (ADT) for clinically node-positive prostate cancer.
Materials and Methods:
Medical records of 60 patients with clinically suspected metastatic lymph nodes on radiological examination were retrospectively analyzed. Eight patients (13.3%) were suspected to have metastatic common iliac or para-aortic lymph nodes. All patients underwent definitive RT with a dose fractionation of 70 Gy in 28 fractions. ADT was initiated 2–3 months before RT and continued for at least 2 years. Biochemical failure rate (BFR), clinical failure rate (CFR), overall survival (OS), and prostate cancer-specific survival (PCSS) were calculated, and genitourinary and gastrointestinal adverse events were recorded.
Results:
The median follow-up period was 5.47 years. The 5-year BFR, CFR, OS, and PCSS rates were 19.1%, 11.3%, 89.0%, and 98.2%, respectively. The median duration of ADT was 2.30 years. BFR and CFR increased after 3 years, and 11 out of 14 biochemical failures occurred after the cessation of ADT. Grade 2 and beyond late genitourinary and gastrointestinal toxicity rates were 5.0% and 13.3%, respectively. However, only two grade 3 adverse events were reported, and no grade 4–5 adverse events were reported. Patients with non-regional lymph node metastases did not have worse BFR, CFR, or adverse event rates.
Conclusion
This study reported the efficacy and tolerable toxicity of hypofractionated definitive RT combined with ADT for clinically node-positive prostate cancer. Additionally, selected patients with adjacent non-regional lymph node metastases might be able to undergo definitive RT combined with ADT.
6.Nomogram Using Prostate Health Index for Predicting Prostate Cancer in the Gray Zone:Prospective, Multicenter Study
Jae Hoon CHUNG ; Jeong Hyun KIM ; Sang Wook LEE ; Hongzoo PARK ; Geehyun SONG ; Wan SONG ; Minyong KANG ; Hyun Hwan SUNG ; Hwang Gyun JEON ; Byong Chang JEONG ; Seong IL SEO ; Hyun Moo LEE ; Seong Soo JEON
The World Journal of Men's Health 2024;42(1):168-177
Purpose:
To create a nomogram that can predict the probability of prostate cancer using prostate health index (PHI) and clinical parameters of patients. And the optimal cut-off value of PHI for prostate cancer was also assessed.
Materials and Methods:
A prospective, multi-center study was conducted. PHI was evaluated prior to biopsy in patients requiring prostate biopsy due to high prostate-specific antigen (PSA). Among screened 1,010 patients, 626 patients with clinically suspected prostate cancer with aged 40 to 85 years, and with PSA levels ranging from 2.5 to 10 ng/mL were analyzed.
Results:
Among 626 patients, 38.82% (243/626) and 22.52% (141/626) were diagnosed with prostate cancer and clinically significant prostate cancer, respectively. In the PSA 2.5 to 4 ng/mL group, the areas under the curve (AUCs) of the nomograms for overall prostate cancer and clinically significant prostate cancer were 0.796 (0.727–0.866; p<0.001), and 0.697 (0.598–0.795; p=0.001), respectively. In the PSA 4 to 10 ng/mL group, the AUCs of nomograms for overall prostate cancer and clinically significant prostate cancer were 0.812 (0.783–0.842; p<0.001), and 0.839 (0.810–0.869; p<0.001), respectively.
Conclusions
Even though external validations are necessary, a nomogram using PHI might improve the prediction of prostate cancer, reducing the need for prostate biopsies.
7.Comparison of Short-Term Outcomes and Safety Profiles between Androgen Deprivation Therapy+Abiraterone/Prednisone and Androgen Deprivation Therapy+Docetaxel in Patients with De Novo Metastatic Hormone-Sensitive Prostate Cancer
Dong Jin PARK ; Tae Gyun KWON ; Jae Young PARK ; Jae Young JOUNG ; Hong Koo HA ; Seong Soo JEON ; Sung-Hoo HONG ; Sungchan PARK ; Seung Hwan LEE ; Jin Seon CHO ; Sung-Woo PARK ; Se Yun KWON ; Jung Ki JO ; Hong Seok PARK ; Sang-Cheol LEE ; Dong Deuk KWON ; Sun Il KIM ; Sang Hyun PARK ; Soodong KIM ; Chang Wook JEONG ; Cheol KWAK ; Seock Hwan CHOI ;
The World Journal of Men's Health 2024;42(3):620-629
Purpose:
This study aimed to compare the short-term outcomes and safety profiles of androgen-deprivation therapy (ADT)+abiraterone/prednisone with those of ADT+docetaxel in patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC).
Materials and Methods:
A web-based database system was established to collect prospective cohort data for patients with mHSPC in Korea. From May 2019 to November 2022, 928 patients with mHSPC from 15 institutions were enrolled. Among these patients, data from 122 patients who received ADT+abiraterone/prednisone or ADT+docetaxel as the primary systemic treatment for mHSPC were collected. The patients were divided into two groups: ADT+abiraterone/prednisone group (n=102) and ADT+docetaxel group (n=20). We compared the demographic characteristics, medical histories, baseline cancer status, initial laboratory tests, metastatic burden, oncological outcomes for mHSPC, progression after mHSPC treatment, adverse effects, follow-up, and survival data between the two groups.
Results:
No significant differences in the demographic characteristics, medical histories, metastatic burden, and baseline cancer status were observed between the two groups. The ADT+abiraterone/prednisone group had a lower prostate-specific antigen (PSA) progression rate (7.8% vs. 30.0%; p=0.011) and lower systemic treatment discontinuation rate (22.5% vs. 45.0%; p=0.037). No significant differences in adverse effects, oncological outcomes, and total follow-up period were observed between the two groups.
Conclusions
ADT+abiraterone/prednisone had lower PSA progression and systemic treatment discontinuation rates than ADT+docetaxel. In conclusion, further studies involving larger, double-blinded randomized trials with extended follow-up periods are necessary.
8.The clinical effectiveness of fused image of single‑photon emission CT and facial CT for the evaluation of degenerative change of mandibular condylar head
Seung‑Hwan JEON ; Seung‑Weon LIM ; Ki‑Hyun JUNG ; Jae‑Yun JEON 1 ; Sang‑Yoon KIM ; Ji‑Young KIM ; Yoon‑Young CHOI ; Kyung‑Gyun HWANG
Maxillofacial Plastic and Reconstructive Surgery 2023;45(1):33-
Background:
The primary objective of this study was to assess the clinical effectiveness of fused images obtained from single-photon emission computed tomography (SPECT) and facial computed tomography (CT) for evaluat‑ ing degenerative changes in the mandibular condylar head. This assessment was accomplished by comparing the Technetium-99 m methylene diphosphonate ( 99m Tc-MDP) uptake ratio with the results of clinical and radiographic findings.
Methods:
The study included 17 patients (3 males and 14 females) with suspected osteoarthritis of the mandibular condyle, totaling 34 temporomandibular joints (TMJs). Based on clinical and radiographic examinations, the TMJs were categorized into four groups: normal (group N), internal derangement (group ID), osteoarthritis (group OA), and osteoarthritis sequelae (group OA seq ). For each patient, bone SPECT and facial CT scans were registered and reconstructed to create fused SPECT/CT images. The 99m Tc-MDP uptake levels in the TMJs were statistically com‑ pared among the four groups.
Results:
The 99m Tc-MDP uptake ratio showed a gradual increase in the order of the following: group N, group OA seq , group ID, and group OA. There was a significant difference observed among groups (pConclusion
Fused SPECT/CT image can be an effective tool for evaluating degenerative changes in the mandibular condylar head. The technique demonstrated the ability to differentiate between normal TMJs and those with internal derangement, osteoarthritis, or osteoarthritis sequelae. This approach holds promise as a valuable method in clinical assessments of TMJ degeneration.
9.Epidemiologic and Clinical Outcomes of Pediatric Renal Tumors in Korea: A Retrospective Analysis of The Korean Pediatric Hematology and Oncology Group (KPHOG) Data
Kyung-Nam KOH ; Jung Woo HAN ; Hyoung Soo CHOI ; Hyoung Jin KANG ; Ji Won LEE ; Keon Hee YOO ; Ki Woong SUNG ; Hong Hoe KOO ; Kyung Taek HONG ; Jung Yoon CHOI ; Sung Han KANG ; Hyery KIM ; Ho Joon IM ; Seung Min HAHN ; Chuhl Joo LYU ; Hee-Jo BAEK ; Hoon KOOK ; Kyung Mi PARK ; Eu Jeen YANG ; Young Tak LIM ; Seongkoo KIM ; Jae Wook LEE ; Nack-Gyun CHUNG ; Bin CHO ; Meerim PARK ; Hyeon Jin PARK ; Byung-Kiu PARK ; Jun Ah LEE ; Jun Eun PARK ; Soon Ki KIM ; Ji Yoon KIM ; Hyo Sun KIM ; Youngeun MA ; Kyung Duk PARK ; Sang Kyu PARK ; Eun Sil PARK ; Ye Jee SHIM ; Eun Sun YOO ; Kyung Ha RYU ; Jae Won YOO ; Yeon Jung LIM ; Hoi Soo YOON ; Mee Jeong LEE ; Jae Min LEE ; In-Sang JEON ; Hye Lim JUNG ; Hee Won CHUEH ; Seunghyun WON ;
Cancer Research and Treatment 2023;55(1):279-290
Purpose:
Renal tumors account for approximately 7% of all childhood cancers. These include Wilms tumor (WT), clear cell sarcoma of the kidney (CCSK), malignant rhabdoid tumor of the kidney (MRTK), renal cell carcinoma (RCC), congenital mesoblastic nephroma (CMN) and other rare tumors. We investigated the epidemiology of pediatric renal tumors in Korea.
Materials and Methods:
From January 2001 to December 2015, data of pediatric patients (0–18 years) newly-diagnosed with renal tumors at 26 hospitals were retrospectively analyzed.
Results:
Among 439 patients (male, 240), the most common tumor was WT (n=342, 77.9%), followed by RCC (n=36, 8.2%), CCSK (n=24, 5.5%), MRTK (n=16, 3.6%), CMN (n=12, 2.7%), and others (n=9, 2.1%). Median age at diagnosis was 27.1 months (range 0-225.5) and median follow-up duration was 88.5 months (range 0-211.6). Overall, 32 patients died, of whom 17, 11, 1, and 3 died of relapse, progressive disease, second malignant neoplasm, and treatment-related mortality. Five-year overall survival and event free survival were 97.2% and 84.8% in WT, 90.6% and 82.1% in RCC, 81.1% and 63.6% in CCSK, 60.3% and 56.2% in MRTK, and 100% and 91.7% in CMN, respectively (p < 0.001).
Conclusion
The pediatric renal tumor types in Korea are similar to those previously reported in other countries. WT accounted for a large proportion and survival was excellent. Non-Wilms renal tumors included a variety of tumors and showed inferior outcome, especially MRTK. Further efforts are necessary to optimize the treatment and analyze the genetic characteristics of pediatric renal tumors in Korea.
10.Identification of Genes Involved in EGF-induced Apoptosis Using CRISPR/Cas9 Knockout Screening: Implications for Novel Therapeutic Targets in EGFR-Overexpressing Cancers
Jae Sik KIM ; Joo Ho LEE ; Sang-Rok JEON ; Yongsub KIM ; Seung Hyuck JEON ; Hong-Gyun WU
Cancer Research and Treatment 2023;55(3):737-745
Purpose:
Exogenous epidermal growth factor (EGF) causes apoptosis in EGF receptor (EGFR)–overexpressing cell lines. The apoptosis-inducing factors could be a therapeutic target. We aimed to determine the mechanism of EGF-induced apoptosis using a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-based knockout screen.
Materials and Methods:
Two-vector system of the human genome-scale CRISPR knockout library v2 was used to target 19,050 genes using 123,411 single guide RNAs (sgRNAs). Recombinant human EGF (100 nM) or distilled water four times was administered to the experimental and control groups, respectively. The read counts of each sgRNA obtained from next-generation sequencing were analyzed using the edgeR algorithm. We used another EGFR-overexpressing cell line (A549) and short hairpin RNAs (shRNAs) targeting five EGF-resistance genes for validation. DUSP1 expression in A431, A549, and HEK293FT cells was calculated using reverse transcription–quantitative polymerase chain reaction.
Results:
We found 77 enriched and 189 depleted genes in the experimental group using the CRISPR-based knockout screen and identified the top five EGF-resistance genes: DDX20, LHFP, REPS1, DUSP1,<.i> and KRTAP10-12. Transfecting shRNAs targeting these genes into A549 cells significantly increased the surviving fractions after EGF treatment, compared with those observed in the control shRNA-transfected cells. The expression ratio of DUSP1 (inhibits ERK signaling) increased in A431 and A549 cells after EGF treatment. However, DUSP1 expression remained unchanged in HEK293FT cells after EGF treatment.
Conclusion
The CRISPR-based knockout screen revealed 266 genes possibly responsible for EGF-induced apoptosis. DUSP1 might be a critical component of EGF-induced apoptosis and a novel target for EGFR-overexpressing cancers.

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