1.Male preference for TERT alterations and HBV integration in young-age HBV-related HCC: implications for sex disparity
Jin Seoub KIM ; Hye Seon KIM ; Kwon Yong TAK ; Ji Won HAN ; Heechul NAM ; Pil Soo SUNG ; Sung Won LEE ; Jung Hyun KWON ; Si Hyun BAE ; Jong Young CHOI ; Seung Kew YOON ; Jeong Won JANG
Clinical and Molecular Hepatology 2025;31(2):509-524
Background/Aims:
Hepatocellular carcinoma (HCC) exhibits significant sex disparities in incidence, yet its molecular mechanisms remain unclear. We explored the role of telomerase reverse transcriptase (TERT) genetic alterations and hepatitis B virus (HBV) integration, both known major contributors to HCC, in sex-specific risk for HBV-related HCC.
Methods:
We examined 310 HBV-related HCC tissues to investigate sex-specific TERT promoter (TERT-pro) mutations and HBV integration profiles, stratified by sex and age, and validated with single-cell RNA sequencing (scRNA-seq) data.
Results:
Tumors predominantly exhibited TERT-pro mutations (26.0% vs. 0%) and HBV-TERT integration (37.0% vs. 3.0%) compared to non-tumorous tissues. While TERT-pro mutations increased with age in both sexes, younger males (≤60 years) showed marked predominance compared to younger females. Males had significantly more HBV integrations at younger ages, while females initially had fewer integrations that gradually increased with age. Younger males' integrations showed significantly greater enrichment in the TERT locus compared to younger females, alongside a preference for promoters, PreS/S regions, and CpG islands. Overall, TERT genetic alterations were significantly sex-differential in younger individuals (75.3% in males vs. 23.1% in females) but not in older individuals (76.9% vs. 83.3%, respectively). These alterations were associated with increased TERT expression. The skewed TERT abnormalities in younger males were further corroborated by independent scRNA-seq data.
Conclusions
Our findings highlight the critical role of TERT alterations and HBV integration patterns in the male predominance of HCC incidence among younger HBV carriers, offering insights for future exploration to optimize sex-specific patient care and HCC surveillance strategies.
2.Male preference for TERT alterations and HBV integration in young-age HBV-related HCC: implications for sex disparity
Jin Seoub KIM ; Hye Seon KIM ; Kwon Yong TAK ; Ji Won HAN ; Heechul NAM ; Pil Soo SUNG ; Sung Won LEE ; Jung Hyun KWON ; Si Hyun BAE ; Jong Young CHOI ; Seung Kew YOON ; Jeong Won JANG
Clinical and Molecular Hepatology 2025;31(2):509-524
Background/Aims:
Hepatocellular carcinoma (HCC) exhibits significant sex disparities in incidence, yet its molecular mechanisms remain unclear. We explored the role of telomerase reverse transcriptase (TERT) genetic alterations and hepatitis B virus (HBV) integration, both known major contributors to HCC, in sex-specific risk for HBV-related HCC.
Methods:
We examined 310 HBV-related HCC tissues to investigate sex-specific TERT promoter (TERT-pro) mutations and HBV integration profiles, stratified by sex and age, and validated with single-cell RNA sequencing (scRNA-seq) data.
Results:
Tumors predominantly exhibited TERT-pro mutations (26.0% vs. 0%) and HBV-TERT integration (37.0% vs. 3.0%) compared to non-tumorous tissues. While TERT-pro mutations increased with age in both sexes, younger males (≤60 years) showed marked predominance compared to younger females. Males had significantly more HBV integrations at younger ages, while females initially had fewer integrations that gradually increased with age. Younger males' integrations showed significantly greater enrichment in the TERT locus compared to younger females, alongside a preference for promoters, PreS/S regions, and CpG islands. Overall, TERT genetic alterations were significantly sex-differential in younger individuals (75.3% in males vs. 23.1% in females) but not in older individuals (76.9% vs. 83.3%, respectively). These alterations were associated with increased TERT expression. The skewed TERT abnormalities in younger males were further corroborated by independent scRNA-seq data.
Conclusions
Our findings highlight the critical role of TERT alterations and HBV integration patterns in the male predominance of HCC incidence among younger HBV carriers, offering insights for future exploration to optimize sex-specific patient care and HCC surveillance strategies.
3.Male preference for TERT alterations and HBV integration in young-age HBV-related HCC: implications for sex disparity
Jin Seoub KIM ; Hye Seon KIM ; Kwon Yong TAK ; Ji Won HAN ; Heechul NAM ; Pil Soo SUNG ; Sung Won LEE ; Jung Hyun KWON ; Si Hyun BAE ; Jong Young CHOI ; Seung Kew YOON ; Jeong Won JANG
Clinical and Molecular Hepatology 2025;31(2):509-524
Background/Aims:
Hepatocellular carcinoma (HCC) exhibits significant sex disparities in incidence, yet its molecular mechanisms remain unclear. We explored the role of telomerase reverse transcriptase (TERT) genetic alterations and hepatitis B virus (HBV) integration, both known major contributors to HCC, in sex-specific risk for HBV-related HCC.
Methods:
We examined 310 HBV-related HCC tissues to investigate sex-specific TERT promoter (TERT-pro) mutations and HBV integration profiles, stratified by sex and age, and validated with single-cell RNA sequencing (scRNA-seq) data.
Results:
Tumors predominantly exhibited TERT-pro mutations (26.0% vs. 0%) and HBV-TERT integration (37.0% vs. 3.0%) compared to non-tumorous tissues. While TERT-pro mutations increased with age in both sexes, younger males (≤60 years) showed marked predominance compared to younger females. Males had significantly more HBV integrations at younger ages, while females initially had fewer integrations that gradually increased with age. Younger males' integrations showed significantly greater enrichment in the TERT locus compared to younger females, alongside a preference for promoters, PreS/S regions, and CpG islands. Overall, TERT genetic alterations were significantly sex-differential in younger individuals (75.3% in males vs. 23.1% in females) but not in older individuals (76.9% vs. 83.3%, respectively). These alterations were associated with increased TERT expression. The skewed TERT abnormalities in younger males were further corroborated by independent scRNA-seq data.
Conclusions
Our findings highlight the critical role of TERT alterations and HBV integration patterns in the male predominance of HCC incidence among younger HBV carriers, offering insights for future exploration to optimize sex-specific patient care and HCC surveillance strategies.
4.Analysis of Response and Progression Patterns of Tyrosine Kinase Inhibitors in Recurrent or Metastatic Adenoid Cystic Carcinoma: A Post Hoc Analysis of Two KCSG Phase II Trials
Youjin KIM ; Bhumsuk KEAM ; Eun Joo KANG ; Jin-Soo KIM ; Hye Ryun KIM ; Keun-Wook LEE ; Jung Hye KWON ; Kyoung Eun LEE ; Yaewon YANG ; Yoon Hee CHOI ; Min Kyoung KIM ; Jun Ho JI ; Tak YUN ; Moon Young CHOI ; Ki Hyeong LEE ; Sung-Bae KIM ; Myung-Ju AHN
Cancer Research and Treatment 2024;56(4):1068-1076
Purpose:
In this study, we evaluated 66 patients diagnosed with adenoid cystic carcinoma (ACC) enrolled in two Korean Cancer Study Group trials to investigate the response and progression patterns in recurrent and/or metastatic ACC treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs).
Materials and Methods:
We evaluated 66 patients diagnosed with ACC who were enrolled in the Korean Cancer Study Group trials. The tumor measurements, clinical data, treatment outcomes, and progression patterns of therapy were analyzed.
Results:
In the 66 patients (53 receiving axitinib and 13 receiving nintedanib), the disease control rate was 61%, and three patients achieved partial response. The median follow-up, median progression-free survival (PFS), overall survival, and 6-month PFS rate were 27.6%, 12.4%, and 18.1% months and 62.1%, respectively. Among 42 patients who experienced progression, 27 (64.3%) showed target lesion progression. Bone metastasis was an independent poor prognostic factor.
Conclusion
Overall, most patients demonstrated stable disease with prolonged PFS; however, prominent target lesion progression occurred in some patients. Thus, PFS may capture VEGFR-TKI efficacy better than the objective response rate.
5.Efficacy of plasma treatment for surface cleansing and osseointegration of sandblasted and acid-etched titanium implants
Gang-Ho BAE ; Won-Tak CHO ; Jong-Ho LEE ; Jung-Bo HUH
The Journal of Advanced Prosthodontics 2024;16(3):189-199
PURPOSE:
This study was conducted to evaluate the effects of plasma treatment of sandblasted and acid-etched (SLA) titanium implants on surface cleansing and osseointegration in a beagle model.
MATERIALS AND METHODS:
For morphological analysis and XPS analysis, scanning electron microscope and x-ray photoelectron spectroscopy were used to analyze the surface topography and chemical compositions of implant before and after plasma treatment. For this animal experiment, twelve SLA titanium implants were divided into two groups:a control group (untreated implants) and a plasma group (implants treated with plasma). Each group was randomly located in the mandibular bone of the beagle dog (n = 6). After 8 weeks, the beagle dogs were sacrificed, and volumetric analysis and histometric analysis were performed within the region of interest.
RESULTS:
In morphological analysis, plasma treatment did not alter the implant surface topography or cause any physical damage. In XPS analysis, the atomic percentage of carbon at the inspection point before the plasma treatment was 34.09%. After the plasma treatment, it was reduced to 18.74%, indicating a 45% reduction in carbon. In volumetric analysis and histometric analysis, the plasma group exhibited relatively higher mean values for new bone volume (NBV), bone to implant contact (BIC), and inter-thread bone density (ITBD) compared to the control group. However, there was no significant difference between the two groups (P > .05).
CONCLUSION
Within the limits of this study, plasma treatment effectively eliminated hydrocarbons without changing the implant surface.
6.A prospective multicenter clinical study on the efficiency of detachable ball- and spring-retained implant prosthesis
Min-Jung KIM ; Won-Tak CHO ; Su-Hyun HWANG ; Ji-Hyeon BAE ; Eun-Bin BAE ; June-Sung SHIM ; Jong-Eun KIM ; Chang-Mo JEONG ; Jung-Bo HUH
The Journal of Advanced Prosthodontics 2023;15(4):202-213
PURPOSE:
This prospective clinical study was conducted to evaluate the clinical usefulness of the freely detachable zirconia ball- and spring-retained implant prosthesis (BSRP) through a comparative analysis of screw- and cement-retained implant prosthesis (SCRP).
MATERIALS AND METHODS:
A multi-center, randomized, prospective clinical study evaluating the clinical usefulness of the detachable zirconia ball- and spring-retained implant prostheses was conducted. Sixty-four implant prostheses in 64 patients were examined. Periodic observational studies were conducted at 0, 3, 6, and 12 months after delivery of the implant prosthesis. Factors such as implant success rate, marginal bone resorption, periodontal pocket depth, plaque and bleeding index, and prosthetic complications were evaluated, respectively.
RESULTS:
During the 1-year observation period, all implants survived without functional problems and clinical mobility, showing a 100% implant success rate. Marginal bone resorption was significantly higher in the SCRP group than in the BSRP group only at the time of implant prosthesis delivery (P = .043). In all observation periods, periodontal pocket depth was slightly higher in the BSRP group than in the SCRP group, but there was no significant difference (P > .05). The modified plaque index (mPI) scores of both groups were moderate. Higher ratio of a score 2 in modified sulcus bleeding index (mBI) was observed in the BSRP group in the 6- and 12-months observation.
CONCLUSION
Within the limitations of this study, the newly developed zirconia ball- and spring-retained implant prosthesis could be considered as an applicable and predictable treatment method along with the existing screw- and cement-retained prosthesis.
7.Comparison of fit and trueness of zirconia crowns fabricated by different combinations of open CAD-CAM systems
Eun-Bin BAE ; Won-Tak CHO ; Do-Hyun PARK ; Su-Hyun HWANG ; So-Hyoun LEE ; Mi-Jung YUN ; Chang-Mo JEONG ; Jung-Bo HUH
The Journal of Advanced Prosthodontics 2023;15(3):155-170
PURPOSE:
. This study aims to clinically compare the fitness and trueness of zirconia crowns fabricated by different combinations of open CAD-CAM systems.
MATERIALS AND METHODS:
. Total of 40 patients were enrolled in this study, and 9 different zirconia crowns were prepared per patient. Each crown was made through the cross-application of 3 different design software (EZIS VR, 3Shape Dental System, Exocad) with 3 different processing devices (Aegis HM, Trione Z, Motion 2). The marginal gap, absolute marginal discrepancy, internal gap(axial, line angle, occlusal) by a silicone replica technique were measured to compare the fit of the crown. The scanned inner and outer surfaces of the crowns were compared to CAD data using 3D metrology software to evaluate trueness.
RESULTS:
. There were significant differences in the marginal gap, absolute marginal discrepancy, axial and line angle internal gap among the groups (P < .05) in the comparison of fit. There was no statistically significant difference among the groups in terms of occlusal internal gap. The trueness ranged from 36.19 to 43.78 μm but there was no statistically significant difference within the groups (P > .05).
CONCLUSION
. All 9 groups showed clinically acceptable level of marginal gaps ranging from 74.26 to 112.20 μm in terms of fit comparison. In the comparison of trueness, no significant difference within each group was spotted. Within the limitation of this study, open CAD-CAM systems used in this study can be assembled properly to fabricate zirconia crown. [J Adv Prosthodont 2023;15:155-70]
8.Comparison of retentive force and wear pattern of Locator® and ADD-TOC attachments combined with CAD-CAM milled bar
Sung-Ki CHAE ; Won-Tak CHO ; Jae-Won CHOI ; Eun-Bin BAE ; Ji-Hyeon BAE ; Gang-Ho BAE ; Jung-Bo HUH
The Journal of Advanced Prosthodontics 2022;14(1):12-21
PURPOSE:
The purpose of this study was to investigate changes in retention and wear pattern of Locator® and ADD-TOC attachments on a digital milled bar by performing chewing simulation and repeated insertion/removal of prostheses in fully edentulous models.
MATERIALS AND METHODS:
Locator (Locator®; Zest Anchors Inc., Escondido, CA, USA) was selected as the control group and ADD-TOC (ADDTOC; PNUAdd Co., Ltd., Busan, Republic of Korea) as the experimental group. A CAD-CAM milled bar was mounted on a master model and 3 threaded holes for connecting a bar attachment was formed using a tap. Locator and ADD-TOC attachments were then attached to the milled bar. Simulated mastication and repeated insertion/removal were performed over 400,000 cyclic loadings and 1,080insertions/removals, respectively. Wear patterns on deformed attachment were investigated by field emission scanning electron microscopy.
RESULTS:
For the ADD-TOC attachments, chewing simulation and repeated insertion/removal resulted in a mean initial retentive force of 24.43 ± 4.89 N, which were significantly lower than that of the Locator attachment, 34.33 ± 8.25 N (P < .05). Amounts of retention loss relative to baseline for the Locator and ADD-TOC attachments were 21.74 ± 7.07 and 8.98 ± 5.76 N (P < .05).
CONCLUSION
CAD-CAM milled bar with the ADD-TOC attachment had a lower initial retentive force than the Locator attachment. However, the ADD-TOC attachment might be suitable for long-term use as it showed less deformation and had a higher retentive force after simulated mastication and insertion/removal repetitions.
9.Clinical Characteristics and Treatment Outcomes of Childhood Acute Promyelocytic Leukemia in Korea: A Nationwide Multicenter Retrospective Study by Korean Pediatric Oncology Study Group
Kyung Mi PARK ; Keon Hee YOO ; Seong Koo KIM ; Jae Wook LEE ; Nack-Gyun CHUNG ; Hee Young JU ; Hong Hoe KOO ; Chuhl Joo LYU ; Seung Min HAN ; Jung Woo HAN ; Jung Yoon CHOI ; Kyung Taek HONG ; Hyoung Jin KANG ; Hee Young SHIN ; Ho Joon IM ; Kyung-Nam KOH ; Hyery KIM ; Hoon KOOK ; Hee Jo BAEK ; Bo Ram KIM ; Eu Jeen YANG ; Jae Young LIM ; Eun Sil PARK ; Eun Jin CHOI ; Sang Kyu PARK ; Jae Min LEE ; Ye Jee SHIM ; Ji Yoon KIM ; Ji Kyoung PARK ; Seom Gim KONG ; Young Bae CHOI ; Bin CHO ; Young Tak LIM
Cancer Research and Treatment 2022;54(1):269-276
Purpose:
Acute promyelocytic leukemia (APL) is a rare disease in children and there are some different characteristics between children and adult. We aimed to evaluate incidence, clinical characteristics and treatment outcomes of pediatric APL in Korea.
Materials and Methods:
Seventy-nine pediatric APL patients diagnosed from January 2009 to December 2016 in 16 tertiary medical centers in Korea were reviewed retrospectively.
Results:
Of 801 acute myeloid leukemia children, 79 (9.9%) were diagnosed with APL. The median age at diagnosis was 10.6 years (range, 1.3 to 18.0). Male and female ratio was 1:0.93. Thirty patients (38.0%) had white blood cell (WBC) count greater than 10×109/L at diagnosis. All patients received induction therapy consisting of all-trans retinoic acid and chemotherapy. Five patients (6.6%) died during induction chemotherapy and 66 patients (86.8%) achieved complete remission (CR) after induction chemotherapy. The causes of death were three intracranial hemorrhage, one cerebral infarction, and one sepsis. Five patients (7.1%) suffered a relapse during or after maintenance chemotherapy. The estimated 4-year event-free survival and overall survival (OS) rates were 82.1%±4.4%, 89.7%±5.1%, respectively. The 4-year OS was significantly higher in patients with initial WBC < 10×109/L than in those with initial WBC ≥ 10×109/L (p=0.020).
Conclusion
This study showed that the CR rates and survival outcomes in Korean pediatric APL patients were relatively good. The initial WBC count was the most important prognostic factor and most causes of death were related to serious bleeding in the early stage of treatment.
10.Mini-implant with additional retentive structure by using digital method
Su-Hyun HWANG ; Eun-Bin BAE ; Won-Tak CHO ; Jung-Bo HUH
The Journal of Korean Academy of Prosthodontics 2022;60(1):119-126
Mini-implant has been reported as an alternative method to conventional diameter implants in the treatment of mandibular anterior region with narrow ridge. However, one-piece type mini-implant showed biological and technical complications, such as peri-implantitis by residual cement and prosthetic detachment. Recently, one-piece type mini-implant with additional retentive structure has been introduced to increase the retention and stability of the mini-implant. The mini-implant is based on spreading the upper retentive structure with a spreader and connected it with the inner surface of the zirconia prosthesis. In two cases, we tried to reduce these complications through the mini-implant on the narrow mandibular anterior region, and it was possible to reduce the overall treatment period through a digital system. In this case report, restoration using the digital mini-implant system showed improvement of patient satisfaction on the aspect of function and esthetic in the narrow mandibular anterior region.

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