1.Gene Expression Alteration by Non-thermal Plasma-Activated Media Treatment in Radioresistant Head and Neck Squamous Cell Carcinoma
Sicong ZHENG ; Yudan PIAO ; Seung-Nam JUNG ; Chan OH ; Mi Ae LIM ; QuocKhanh NGUYEN ; Shan SHEN ; Se-Hee PARK ; Shengzhe CUI ; Shuyu PIAO ; Young Il KIM ; Ji Won KIM ; Ho-Ryun WON ; Jae Won CHANG ; Yujuan SHAN ; Lihua LIU ; Bon Seok KOO
Clinical and Experimental Otorhinolaryngology 2025;18(1):73-87
Objectives:
. Head and neck squamous cell carcinoma (HNSCC) exhibits high recurrence rates, particularly in cases of radioresistant HNSCC (RR-HNSCC). Non-thermal plasma (NTP) therapy effectively suppresses the progression of HNSCC. However, the therapeutic mechanisms of NTP therapy in treating RR-HNSCC are not well understood. In this study, we explored the regulatory role of NTP in the RR-HNSCC signaling pathway and identified its signature genes.
Methods:
. After constructing two RR-HNSCC cell lines, we prepared cell lysates from cells treated or not treated with NTP-activated media (NTPAM) and performed RNA sequencing to determine their mRNA expression profiles. Based on the RNA sequencing results, we identified differentially expressed genes (DEGs), followed by a bioinformatics analysis to identify candidate molecules potentially associated with NTPAM therapy for RR-HNSCC.
Results:
. NTPAM reduced RR-HNSCC cell viability in vitro. RNA sequencing results indicated that NTPAM treatment activated the reactive oxygen species (ROS) pathway and induced ferroptosis in RR-HNSCC cell lines. Among the 1,924 genes correlated with radiation treatment, eight showed statistical significance in both the cell lines and The Cancer Genome Atlas (TCGA) cohort. Only five genes—ABCC3, DUSP16, PDGFB, RAF1, and THBS1—showed consistent results between the NTPAM data sequencing and TCGA data. LASSO regression analysis revealed that five genes were associated with cancer prognosis, with a hazard ratio of 2.26. In RR-HNSCC cells, NTPAM affected DUSP16, PDGFB, and THBS1 as activated markers within 6 hours, and this effect persisted for 12 hours. Furthermore, enrichment analysis indicated that these three DEGs were associated with the extracellular matrix, transforming growth factor-beta, phosphoinositide 3-kinase/protein kinase B, and mesenchymal-epithelial transition factor pathways.
Conclusion
. NTPAM therapy exerts cytotoxic effects in RR-HNSCC cell lines by inducing specific ROS-mediated ferroptosis. DUSP16, PDGFB, and THBS1 were identified as crucial targets for reversing the radiation resistance induced by NTPAM therapy, providing insights into the mechanisms and clinical applications of NTPAM treatment in RR-HNSCC.
2.Gene Expression Alteration by Non-thermal Plasma-Activated Media Treatment in Radioresistant Head and Neck Squamous Cell Carcinoma
Sicong ZHENG ; Yudan PIAO ; Seung-Nam JUNG ; Chan OH ; Mi Ae LIM ; QuocKhanh NGUYEN ; Shan SHEN ; Se-Hee PARK ; Shengzhe CUI ; Shuyu PIAO ; Young Il KIM ; Ji Won KIM ; Ho-Ryun WON ; Jae Won CHANG ; Yujuan SHAN ; Lihua LIU ; Bon Seok KOO
Clinical and Experimental Otorhinolaryngology 2025;18(1):73-87
Objectives:
. Head and neck squamous cell carcinoma (HNSCC) exhibits high recurrence rates, particularly in cases of radioresistant HNSCC (RR-HNSCC). Non-thermal plasma (NTP) therapy effectively suppresses the progression of HNSCC. However, the therapeutic mechanisms of NTP therapy in treating RR-HNSCC are not well understood. In this study, we explored the regulatory role of NTP in the RR-HNSCC signaling pathway and identified its signature genes.
Methods:
. After constructing two RR-HNSCC cell lines, we prepared cell lysates from cells treated or not treated with NTP-activated media (NTPAM) and performed RNA sequencing to determine their mRNA expression profiles. Based on the RNA sequencing results, we identified differentially expressed genes (DEGs), followed by a bioinformatics analysis to identify candidate molecules potentially associated with NTPAM therapy for RR-HNSCC.
Results:
. NTPAM reduced RR-HNSCC cell viability in vitro. RNA sequencing results indicated that NTPAM treatment activated the reactive oxygen species (ROS) pathway and induced ferroptosis in RR-HNSCC cell lines. Among the 1,924 genes correlated with radiation treatment, eight showed statistical significance in both the cell lines and The Cancer Genome Atlas (TCGA) cohort. Only five genes—ABCC3, DUSP16, PDGFB, RAF1, and THBS1—showed consistent results between the NTPAM data sequencing and TCGA data. LASSO regression analysis revealed that five genes were associated with cancer prognosis, with a hazard ratio of 2.26. In RR-HNSCC cells, NTPAM affected DUSP16, PDGFB, and THBS1 as activated markers within 6 hours, and this effect persisted for 12 hours. Furthermore, enrichment analysis indicated that these three DEGs were associated with the extracellular matrix, transforming growth factor-beta, phosphoinositide 3-kinase/protein kinase B, and mesenchymal-epithelial transition factor pathways.
Conclusion
. NTPAM therapy exerts cytotoxic effects in RR-HNSCC cell lines by inducing specific ROS-mediated ferroptosis. DUSP16, PDGFB, and THBS1 were identified as crucial targets for reversing the radiation resistance induced by NTPAM therapy, providing insights into the mechanisms and clinical applications of NTPAM treatment in RR-HNSCC.
3.Gene Expression Alteration by Non-thermal Plasma-Activated Media Treatment in Radioresistant Head and Neck Squamous Cell Carcinoma
Sicong ZHENG ; Yudan PIAO ; Seung-Nam JUNG ; Chan OH ; Mi Ae LIM ; QuocKhanh NGUYEN ; Shan SHEN ; Se-Hee PARK ; Shengzhe CUI ; Shuyu PIAO ; Young Il KIM ; Ji Won KIM ; Ho-Ryun WON ; Jae Won CHANG ; Yujuan SHAN ; Lihua LIU ; Bon Seok KOO
Clinical and Experimental Otorhinolaryngology 2025;18(1):73-87
Objectives:
. Head and neck squamous cell carcinoma (HNSCC) exhibits high recurrence rates, particularly in cases of radioresistant HNSCC (RR-HNSCC). Non-thermal plasma (NTP) therapy effectively suppresses the progression of HNSCC. However, the therapeutic mechanisms of NTP therapy in treating RR-HNSCC are not well understood. In this study, we explored the regulatory role of NTP in the RR-HNSCC signaling pathway and identified its signature genes.
Methods:
. After constructing two RR-HNSCC cell lines, we prepared cell lysates from cells treated or not treated with NTP-activated media (NTPAM) and performed RNA sequencing to determine their mRNA expression profiles. Based on the RNA sequencing results, we identified differentially expressed genes (DEGs), followed by a bioinformatics analysis to identify candidate molecules potentially associated with NTPAM therapy for RR-HNSCC.
Results:
. NTPAM reduced RR-HNSCC cell viability in vitro. RNA sequencing results indicated that NTPAM treatment activated the reactive oxygen species (ROS) pathway and induced ferroptosis in RR-HNSCC cell lines. Among the 1,924 genes correlated with radiation treatment, eight showed statistical significance in both the cell lines and The Cancer Genome Atlas (TCGA) cohort. Only five genes—ABCC3, DUSP16, PDGFB, RAF1, and THBS1—showed consistent results between the NTPAM data sequencing and TCGA data. LASSO regression analysis revealed that five genes were associated with cancer prognosis, with a hazard ratio of 2.26. In RR-HNSCC cells, NTPAM affected DUSP16, PDGFB, and THBS1 as activated markers within 6 hours, and this effect persisted for 12 hours. Furthermore, enrichment analysis indicated that these three DEGs were associated with the extracellular matrix, transforming growth factor-beta, phosphoinositide 3-kinase/protein kinase B, and mesenchymal-epithelial transition factor pathways.
Conclusion
. NTPAM therapy exerts cytotoxic effects in RR-HNSCC cell lines by inducing specific ROS-mediated ferroptosis. DUSP16, PDGFB, and THBS1 were identified as crucial targets for reversing the radiation resistance induced by NTPAM therapy, providing insights into the mechanisms and clinical applications of NTPAM treatment in RR-HNSCC.
4.Discordance Between Angiographic Assessment and Fractional Flow Reserve or Intravascular Ultrasound in Intermediate Coronary Lesions: A Post-hoc Analysis of the FLAVOUR Trial
Jung-Hee LEE ; Sung Gyun AHN ; Ho Sung JEON ; Jun-Won LEE ; Young Jin YOUN ; Jinlong ZHANG ; Xinyang HU ; Jian’an WANG ; Joo Myung LEE ; Joo-Yong HAHN ; Chang-Wook NAM ; Joon-Hyung DOH ; Bong-Ki LEE ; Weon KIM ; Jinyu HUANG ; Fan JIANG ; Hao ZHOU ; Peng CHEN ; Lijiang TANG ; Wenbing JIANG ; Xiaomin CHEN ; Wenming HE ; Myeong-Ho YOON ; Seung-Jea TAHK ; Ung KIM ; You-Jeong KI ; Eun-Seok SHIN ; Doyeon HWANG ; Jeehoon KANG ; Hyo-Soo KIM ; Bon-Kwon KOO
Korean Circulation Journal 2024;54(8):485-496
Background and Objectives:
Angiographic assessment of coronary stenosis severity using quantitative coronary angiography (QCA) is often inconsistent with that based on fractional flow reserve (FFR) or intravascular ultrasound (IVUS). We investigated the incidence of discrepancies between QCA and FFR or IVUS, and the outcomes of FFR- and IVUS-guided strategies in discordant coronary lesions.
Methods:
This study was a post-hoc analysis of the FLAVOUR study. We used a QCA-derived diameter stenosis (DS) of 60% or greater, the highest tertile, to classify coronary lesions as concordant or discordant with FFR or IVUS criteria for percutaneous coronary intervention (PCI). The patient-oriented composite outcome (POCO) was defined as a composite of death, myocardial infarction, or revascularization at 24 months.
Results:
The discordance rate between QCA and FFR or IVUS was 30.2% (n=551). The QCAFFR discordance rate was numerically lower than the QCA-IVUS discordance rate (28.2% vs. 32.4%, p=0.050). In 200 patients with ≥60% DS, PCI was deferred according to negative FFR (n=141) and negative IVUS (n=59) (15.3% vs. 6.5%, p<0.001). The POCO incidence was comparable between the FFR- and IVUS-guided deferral strategies (5.9% vs. 3.4%, p=0.479).Conversely, 351 patients with DS <60% underwent PCI according to positive FFR (n=118) and positive IVUS (n=233) (12.8% vs. 25.9%, p<0.001). FFR- and IVUS-guided PCI did not differ in the incidence of POCO (9.5% vs. 6.5%, p=0.294).
Conclusions
The proportion of QCA-FFR or IVUS discordance was approximately one third for intermediate coronary lesions. FFR- or IVUS-guided strategies for these lesions were comparable with respect to POCO at 24 months.
5.Discordance Between Angiographic Assessment and Fractional Flow Reserve or Intravascular Ultrasound in Intermediate Coronary Lesions: A Post-hoc Analysis of the FLAVOUR Trial
Jung-Hee LEE ; Sung Gyun AHN ; Ho Sung JEON ; Jun-Won LEE ; Young Jin YOUN ; Jinlong ZHANG ; Xinyang HU ; Jian’an WANG ; Joo Myung LEE ; Joo-Yong HAHN ; Chang-Wook NAM ; Joon-Hyung DOH ; Bong-Ki LEE ; Weon KIM ; Jinyu HUANG ; Fan JIANG ; Hao ZHOU ; Peng CHEN ; Lijiang TANG ; Wenbing JIANG ; Xiaomin CHEN ; Wenming HE ; Myeong-Ho YOON ; Seung-Jea TAHK ; Ung KIM ; You-Jeong KI ; Eun-Seok SHIN ; Doyeon HWANG ; Jeehoon KANG ; Hyo-Soo KIM ; Bon-Kwon KOO
Korean Circulation Journal 2024;54(8):485-496
Background and Objectives:
Angiographic assessment of coronary stenosis severity using quantitative coronary angiography (QCA) is often inconsistent with that based on fractional flow reserve (FFR) or intravascular ultrasound (IVUS). We investigated the incidence of discrepancies between QCA and FFR or IVUS, and the outcomes of FFR- and IVUS-guided strategies in discordant coronary lesions.
Methods:
This study was a post-hoc analysis of the FLAVOUR study. We used a QCA-derived diameter stenosis (DS) of 60% or greater, the highest tertile, to classify coronary lesions as concordant or discordant with FFR or IVUS criteria for percutaneous coronary intervention (PCI). The patient-oriented composite outcome (POCO) was defined as a composite of death, myocardial infarction, or revascularization at 24 months.
Results:
The discordance rate between QCA and FFR or IVUS was 30.2% (n=551). The QCAFFR discordance rate was numerically lower than the QCA-IVUS discordance rate (28.2% vs. 32.4%, p=0.050). In 200 patients with ≥60% DS, PCI was deferred according to negative FFR (n=141) and negative IVUS (n=59) (15.3% vs. 6.5%, p<0.001). The POCO incidence was comparable between the FFR- and IVUS-guided deferral strategies (5.9% vs. 3.4%, p=0.479).Conversely, 351 patients with DS <60% underwent PCI according to positive FFR (n=118) and positive IVUS (n=233) (12.8% vs. 25.9%, p<0.001). FFR- and IVUS-guided PCI did not differ in the incidence of POCO (9.5% vs. 6.5%, p=0.294).
Conclusions
The proportion of QCA-FFR or IVUS discordance was approximately one third for intermediate coronary lesions. FFR- or IVUS-guided strategies for these lesions were comparable with respect to POCO at 24 months.
6.Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Part III. Management of Advanced Differentiated Thyroid Cancers - Chapter 1-2. Locally Recurred/Persistent Thyroid Cancer Management Strategies 2024
Ho-Ryun WON ; Min Kyoung LEE ; Ho-Cheol KANG ; Bon Seok KOO ; Hyungju KWON ; Sun Wook KIM ; Won Woong KIM ; Jung-Han KIM ; Young Joo PARK ; Jun-Ook PARK ; Young Shin SONG ; Seung Hoon WOO ; Chang Hwan RYU ; Eun Kyung LEE ; Joon-Hyop LEE ; Ji Ye LEE ; Cho Rok LEE ; Dong-Jun LIM ; Jae-Yol LIM ; Yun Jae CHUNG ; Kyorim BACK ; Dong Gyu NA ;
International Journal of Thyroidology 2024;17(1):147-152
These guidelines aim to establish the standard practice for diagnosing and treating patients with differentiated thyroid cancer (DTC). Based on the Korean Thyroid Association (KTA) Guidelines on DTC management, the “Treatment of Advanced DTC” section was revised in 2024 and has been provided through this chapter. Especially, this chapter covers surgical and nonsurgical treatments for the local (previous surgery site) or regional (cervical lymph node metastasis) recurrences. After drafting the guidelines, it was finalized by collecting opinions from KTA members and related societies. Surgical resection is the preferred treatment for local or regional recurrence of advanced DTC. If surgical resection is not possible, nonsurgical resection treatment under ultrasonography guidance may be considered as an alternative treatment for local or regional recurrence of DTC. Furthermore, if residual lesions are suspected even after surgical resection or respiratory-digestive organ invasion, additional radioactive iodine and external radiation treatments are considered.
7.Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Part I. Initial Management of Differentiated Thyroid Cancers - Chapter 3. Perioperative Assessment of Surgical Complications 2024
Chang Hwan RYU ; Ho-Cheol KANG ; Bon Seok KOO ; Sun Wook KIM ; Dong Gyu NA ; Young Joo PARK ; Jun-Ook PARK ; Young Shin SONG ; Seung Hoon WOO ; Ho-Ryun WON ; Sihoon LEE ; Eun Kyung LEE ; Dong-Jun LIM ; Yun Kyung JEON ; Yun Jae CHUNG ; Jae-Yol LIM ; A Ram HONG ;
International Journal of Thyroidology 2024;17(1):53-60
Thyroid surgery complications include voice change, vocal fold paralysis, and hypoparathyroidism. The voice status should be evaluated pre- and post-surgery. In patients with voice change, laryngeal visualization is needed.Intraoperative neuromonitoring helps reduce recurrent laryngeal nerve injury. The measurement of serum calcium, parathyroid hormone, and 25-hydroxyvitamin D levels is recommended to evaluate perioperative parathyroid function and prescribe supplementation preoperatively if necessary. For postoperative hypoparathyroidism, vitamin D and oral calcium supplementation are indicated based on serum parathyroid hormone and calcium levels and the severity of symptoms or signs of hypocalcemia. If long-term treatment is required, the appropriateness of treatment should be evaluated based on the disease itself and the consideration of potential benefits and harms from long-term replacement.
8.Korean Thyroid Association Management Guidelines for Patients with Thyroid Nodules 2024
Young Joo PARK ; Eun Kyung LEE ; Young Shin SONG ; Su Hwan KANG ; Bon Seok KOO ; Sun Wook KIM ; Dong Gyu NA ; Seung-Kuk BAEK ; So Won OH ; Min Kyoung LEE ; Sang-Woo LEE ; Young Ah LEE ; Yong Sang LEE ; Ji Ye LEE ; Dong-Jun LIM ; Leehi JOO ; Yuh-Seog JUNG ; Chan Kwon JUNG ; Yoon Young CHO ; Yun Jae CHUNG ; Won Bae KIM ; Ka Hee YI ; Ho-Cheol KANG ; Do Joon PARK
International Journal of Thyroidology 2024;17(1):208-244
Thyroid nodules represent a prevalent condition that is detectable via palpation or ultrasound. In recent years, there has been a paradigm shift toward enhanced diagnostic precision and less aggressive therapeutic approaches, highlighting the growing necessity for tailored clinical recommendations to optimize patient outcomes. The Korean Thyroid Association (KTA) has developed guidelines for managing patients with thyroid nodules, following a comprehensive review by task force members of the relevant literature identified via electronic database searches. The recommendations are provided with a level of recommendation for each section. The guidelines encompass thyroid cancer screening in high-risk groups, appropriate diagnostic methods for thyroid nodules, role of pathologic and molecular marker testing in making a diagnosis, long-term follow-up and treatment of benign thyroid nodules, and special considerations for pregnant women. The major revisions that were made in the 2023 guidelines were the definition of high-risk groups for thyroid cancer screening, application of the revised Korean Thyroid Imaging Reporting and Data System (K-TIRADS), addition of the role of core needle biopsy and molecular marker tests, application of active surveillance in patients with low-risk papillary thyroid microcarcinoma, and updated indications for nonsurgical treatment of benign thyroid nodules. In the 2024 revision of the KTA guidelines for thyroid cancer, the evidence for some recommendations has been updated to address the tumor size in the context of active surveillance in patients with low-risk thyroid cancer and the surgical size cutoff. These evidence-based recommendations serve to inform clinical decision-making in the management of thyroid nodules, thereby facilitating the delivery of optimal and efficacious treatments to patients.
9.Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Part V. Pediatric Differentiated Thyroid Cancer 2024
Jung-Eun MOON ; So Won OH ; Ho-Cheol KANG ; Bon Seok KOO ; Keunyoung KIM ; Sun Wook KIM ; Won Woong KIM ; Jung-Han KIM ; Dong Gyu NA ; Sohyun PARK ; Young Joo PARK ; Jun-Ook PARK ; Ji-In BANG ; Kyorim BACK ; Youngduk SEO ; Young Shin SONG ; Seung Hoon WOO ; Ho-Ryun WON ; Chang Hwan RYU ; Sang-Woo LEE ; Eun Kyung LEE ; Joon-Hyop LEE ; Jieun LEE ; Cho Rok LEE ; Dong-Jun LIM ; Jae-Yol LIM ; Ari CHONG ; Yun Jae CHUNG ; Chae Moon HONG ; Hyungju KWON ; Young Ah LEE ;
International Journal of Thyroidology 2024;17(1):193-207
Pediatric differentiated thyroid cancers (DTCs), mostly papillary thyroid cancer (PTC, 80-90%), are diagnosed at more advanced stages with larger tumor sizes and higher rates of locoregional and/or lung metastasis. Despite the higher recurrence rates of pediatric cancers than of adult thyroid cancers, pediatric patients demonstrate a lower mortality rate and more favorable prognosis. Considering the more advanced stage at diagnosis in pediatric patients, preoperative evaluation is crucial to determine the extent of surgery required. Furthermore, if hereditary tumor syndrome is suspected, genetic testing is required. Recommendations for pediatric DTCs focus on the surgical principles, radioiodine therapy according to the postoperative risk level, treatment and follow-up of recurrent or persistent diseases, and treatment of patients with radioiodine-refractory PTCs on the basis of genetic drivers that are unique to pediatric patients.
10.Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Overview and Summary 2024
Young Joo PARK ; Eun Kyung LEE ; Young Shin SONG ; Bon Seok KOO ; Hyungju KWON ; Keunyoung KIM ; Mijin KIM ; Bo Hyun KIM ; Won Gu KIM ; Won Bae KIM ; Won Woong KIM ; Jung-Han KIM ; Hee Kyung KIM ; Hee Young NA ; Shin Je MOON ; Jung-Eun MOON ; Sohyun PARK ; Jun-Ook PARK ; Ji-In BANG ; Kyorim BACK ; Youngduk SEO ; Dong Yeob SHIN ; Su-Jin SHIN ; Hwa Young AHN ; So Won OH ; Seung Hoon WOO ; Ho-Ryun WON ; Chang Hwan RYU ; Jee Hee YOON ; Ka Hee YI ; Min Kyoung LEE ; Sang-Woo LEE ; Seung Eun LEE ; Sihoon LEE ; Young Ah LEE ; Joon-Hyop LEE ; Ji Ye LEE ; Jieun LEE ; Cho Rok LEE ; Dong-Jun LIM ; Jae-Yol LIM ; Yun Kyung JEON ; Kyong Yeun JUNG ; Ari CHONG ; Yun Jae CHUNG ; Chan Kwon JUNG ; Kwanhoon JO ; Yoon Young CHO ; A Ram HONG ; Chae Moon HONG ; Ho-Cheol KANG ; Sun Wook KIM ; Woong Youn CHUNG ; Do Joon PARK ; Dong Gyu NA ;
International Journal of Thyroidology 2024;17(1):1-20
Differentiated thyroid cancer demonstrates a wide range of clinical presentations, from very indolent cases to those with an aggressive prognosis. Therefore, diagnosing and treating each cancer appropriately based on its risk status is important. The Korean Thyroid Association (KTA) has provided and amended the clinical guidelines for thyroid cancer management since 2007. The main changes in this revised 2024 guideline include 1) individualization of surgical extent according to pathological tests and clinical findings, 2) application of active surveillance in low-risk papillary thyroid microcarcinoma, 3) indications for minimally invasive surgery, 4) adoption of World Health Organization pathological diagnostic criteria and definition of terminology in Korean, 5) update on literature evidence of recurrence risk for initial risk stratification, 6) addition of the role of molecular testing, 7) addition of definition of initial risk stratification and targeting thyroid stimulating hormone (TSH) concentrations according to ongoing risk stratification (ORS), 8) addition of treatment of perioperative hypoparathyroidism, 9) update on systemic chemotherapy, and 10) addition of treatment for pediatric patients with thyroid cancer.

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