1.Decline in sestrin 2 expression during aging shifts mesenchymal stem cell differentiation from osteogenic to adipogenic lineage
Do Yeun KIM ; Hyun-Jung PARK ; Jeong-Hwa BAEK
International Journal of Oral Biology 2024;49(3):69-78
Sestrin 2 (SESN2) is a member of the sestrin family of stress-induced proteins that negatively regulate agingassociated biological processes. This study aims to investigate the role of SESN2 in regulating the differentiation potential and senescence of mesenchymal stem cells (MSCs) derived from young and elderly donors. Bulk RNA sequencing revealed a common decline in the SESN2 mRNA levels in MSCs from elderly individuals, which was confirmed via reverse transcription-polymerase chain reaction and western blot analyses. SESN2 knockdown in MSCs from young donors resulted in phenotypic changes similar to those in MSCs from elderly donors, including an enhanced expression of senescence and adipogenic markers and diminished expression of osteogenic markers.To confirm the effect of decreased SESN2 expression on osteogenic and adipogenic differentiation, we induced Sesn2 knockdown in mouse bone marrow-derived MSCs. Sesn2 knockdown suppressed the mRNA expression of osteogenic marker genes, alkaline phosphatase activity, and matrix mineralization. Furthermore, Sesn2 knockdown enhanced mRNA expression of the adipogenic marker genes and intracellular lipid accumulation. These results suggest that a decline in SESN2 expression during aging contributes to the shift of MSC differentiation from osteogenic to adipogenic lineage.
2.Distinct Impacts of Clinicopathological and Mutational Profiles on Long-Term Survival and Recurrence in Medullary Thyroid Carcinoma
Moon Young OH ; Kyong Yeun JUNG ; Hoonsung CHOI ; Young Jun CHAI ; Sun Wook CHO ; Su-jin KIM ; Kyu Eun LEE ; Eun-Jae CHUNG ; Do Joon PARK ; Young Joo PARK ; Han-Kwang YANG
Endocrinology and Metabolism 2024;39(6):877-890
Background:
Medullary thyroid carcinoma (MTC) has a poorer prognosis than differentiated thyroid cancers; however, comprehensive data on the long-term outcomes of MTC remain scarce. This study investigated the extended clinical outcomes of MTC and aimed to identify prognostic factors.
Methods:
Patients diagnosed with MTC between 1980 and 2020 were retrospectively reviewed. Their clinical characteristics, longterm clinical outcomes, and prognostic factors for recurrence and mortality were analyzed.
Results:
The study included 226 patients (144 women, 82 men). The disease-specific survival (DSS) rates for all MTC patients at 5-, 10-, 20-, and 30-year intervals were 92.7%, 89.4%, 74.3%, and 68.1%, respectively. The recurrence-free survival (RFS) rates were 71.1%, 56.1%, 40.2%, and 32.1% at these intervals. DSS was comparable between the groups from 1980–2009 and 2010–2020 (P=0.995); however, the 1980–2009 group had significantly lower RFS rates (P=0.031). The 2010–2020 group exhibited greater extents of surgical and lymph node dissection (P=0.003) and smaller tumors (P=0.003). Multivariate analysis identified extrathyroidal extension as the strongest prognostic factor for both RFS and DSS. Age >55 years and tumor size of ≥2 cm were also significant prognostic factors for DSS, while hereditary disease and lymph node metastasis were significant for RFS. Survival analysis after propensity-score matching of rearranged during transfection (RET)-negative and non-screened RET-positive groups showed comparable DSS but longer RFS in the RET-negative group.
Conclusion
Extrathyroidal extension was identified as the strongest prognostic factor for RFS and DSS. Older age and larger tumor size were associated with decreased DSS, while RET mutation and lymph node metastasis significantly impacted RFS.
3.Distinct Impacts of Clinicopathological and Mutational Profiles on Long-Term Survival and Recurrence in Medullary Thyroid Carcinoma
Moon Young OH ; Kyong Yeun JUNG ; Hoonsung CHOI ; Young Jun CHAI ; Sun Wook CHO ; Su-jin KIM ; Kyu Eun LEE ; Eun-Jae CHUNG ; Do Joon PARK ; Young Joo PARK ; Han-Kwang YANG
Endocrinology and Metabolism 2024;39(6):877-890
Background:
Medullary thyroid carcinoma (MTC) has a poorer prognosis than differentiated thyroid cancers; however, comprehensive data on the long-term outcomes of MTC remain scarce. This study investigated the extended clinical outcomes of MTC and aimed to identify prognostic factors.
Methods:
Patients diagnosed with MTC between 1980 and 2020 were retrospectively reviewed. Their clinical characteristics, longterm clinical outcomes, and prognostic factors for recurrence and mortality were analyzed.
Results:
The study included 226 patients (144 women, 82 men). The disease-specific survival (DSS) rates for all MTC patients at 5-, 10-, 20-, and 30-year intervals were 92.7%, 89.4%, 74.3%, and 68.1%, respectively. The recurrence-free survival (RFS) rates were 71.1%, 56.1%, 40.2%, and 32.1% at these intervals. DSS was comparable between the groups from 1980–2009 and 2010–2020 (P=0.995); however, the 1980–2009 group had significantly lower RFS rates (P=0.031). The 2010–2020 group exhibited greater extents of surgical and lymph node dissection (P=0.003) and smaller tumors (P=0.003). Multivariate analysis identified extrathyroidal extension as the strongest prognostic factor for both RFS and DSS. Age >55 years and tumor size of ≥2 cm were also significant prognostic factors for DSS, while hereditary disease and lymph node metastasis were significant for RFS. Survival analysis after propensity-score matching of rearranged during transfection (RET)-negative and non-screened RET-positive groups showed comparable DSS but longer RFS in the RET-negative group.
Conclusion
Extrathyroidal extension was identified as the strongest prognostic factor for RFS and DSS. Older age and larger tumor size were associated with decreased DSS, while RET mutation and lymph node metastasis significantly impacted RFS.
4.Decline in sestrin 2 expression during aging shifts mesenchymal stem cell differentiation from osteogenic to adipogenic lineage
Do Yeun KIM ; Hyun-Jung PARK ; Jeong-Hwa BAEK
International Journal of Oral Biology 2024;49(3):69-78
Sestrin 2 (SESN2) is a member of the sestrin family of stress-induced proteins that negatively regulate agingassociated biological processes. This study aims to investigate the role of SESN2 in regulating the differentiation potential and senescence of mesenchymal stem cells (MSCs) derived from young and elderly donors. Bulk RNA sequencing revealed a common decline in the SESN2 mRNA levels in MSCs from elderly individuals, which was confirmed via reverse transcription-polymerase chain reaction and western blot analyses. SESN2 knockdown in MSCs from young donors resulted in phenotypic changes similar to those in MSCs from elderly donors, including an enhanced expression of senescence and adipogenic markers and diminished expression of osteogenic markers.To confirm the effect of decreased SESN2 expression on osteogenic and adipogenic differentiation, we induced Sesn2 knockdown in mouse bone marrow-derived MSCs. Sesn2 knockdown suppressed the mRNA expression of osteogenic marker genes, alkaline phosphatase activity, and matrix mineralization. Furthermore, Sesn2 knockdown enhanced mRNA expression of the adipogenic marker genes and intracellular lipid accumulation. These results suggest that a decline in SESN2 expression during aging contributes to the shift of MSC differentiation from osteogenic to adipogenic lineage.
5.Distinct Impacts of Clinicopathological and Mutational Profiles on Long-Term Survival and Recurrence in Medullary Thyroid Carcinoma
Moon Young OH ; Kyong Yeun JUNG ; Hoonsung CHOI ; Young Jun CHAI ; Sun Wook CHO ; Su-jin KIM ; Kyu Eun LEE ; Eun-Jae CHUNG ; Do Joon PARK ; Young Joo PARK ; Han-Kwang YANG
Endocrinology and Metabolism 2024;39(6):877-890
Background:
Medullary thyroid carcinoma (MTC) has a poorer prognosis than differentiated thyroid cancers; however, comprehensive data on the long-term outcomes of MTC remain scarce. This study investigated the extended clinical outcomes of MTC and aimed to identify prognostic factors.
Methods:
Patients diagnosed with MTC between 1980 and 2020 were retrospectively reviewed. Their clinical characteristics, longterm clinical outcomes, and prognostic factors for recurrence and mortality were analyzed.
Results:
The study included 226 patients (144 women, 82 men). The disease-specific survival (DSS) rates for all MTC patients at 5-, 10-, 20-, and 30-year intervals were 92.7%, 89.4%, 74.3%, and 68.1%, respectively. The recurrence-free survival (RFS) rates were 71.1%, 56.1%, 40.2%, and 32.1% at these intervals. DSS was comparable between the groups from 1980–2009 and 2010–2020 (P=0.995); however, the 1980–2009 group had significantly lower RFS rates (P=0.031). The 2010–2020 group exhibited greater extents of surgical and lymph node dissection (P=0.003) and smaller tumors (P=0.003). Multivariate analysis identified extrathyroidal extension as the strongest prognostic factor for both RFS and DSS. Age >55 years and tumor size of ≥2 cm were also significant prognostic factors for DSS, while hereditary disease and lymph node metastasis were significant for RFS. Survival analysis after propensity-score matching of rearranged during transfection (RET)-negative and non-screened RET-positive groups showed comparable DSS but longer RFS in the RET-negative group.
Conclusion
Extrathyroidal extension was identified as the strongest prognostic factor for RFS and DSS. Older age and larger tumor size were associated with decreased DSS, while RET mutation and lymph node metastasis significantly impacted RFS.
6.Distinct Impacts of Clinicopathological and Mutational Profiles on Long-Term Survival and Recurrence in Medullary Thyroid Carcinoma
Moon Young OH ; Kyong Yeun JUNG ; Hoonsung CHOI ; Young Jun CHAI ; Sun Wook CHO ; Su-jin KIM ; Kyu Eun LEE ; Eun-Jae CHUNG ; Do Joon PARK ; Young Joo PARK ; Han-Kwang YANG
Endocrinology and Metabolism 2024;39(6):877-890
Background:
Medullary thyroid carcinoma (MTC) has a poorer prognosis than differentiated thyroid cancers; however, comprehensive data on the long-term outcomes of MTC remain scarce. This study investigated the extended clinical outcomes of MTC and aimed to identify prognostic factors.
Methods:
Patients diagnosed with MTC between 1980 and 2020 were retrospectively reviewed. Their clinical characteristics, longterm clinical outcomes, and prognostic factors for recurrence and mortality were analyzed.
Results:
The study included 226 patients (144 women, 82 men). The disease-specific survival (DSS) rates for all MTC patients at 5-, 10-, 20-, and 30-year intervals were 92.7%, 89.4%, 74.3%, and 68.1%, respectively. The recurrence-free survival (RFS) rates were 71.1%, 56.1%, 40.2%, and 32.1% at these intervals. DSS was comparable between the groups from 1980–2009 and 2010–2020 (P=0.995); however, the 1980–2009 group had significantly lower RFS rates (P=0.031). The 2010–2020 group exhibited greater extents of surgical and lymph node dissection (P=0.003) and smaller tumors (P=0.003). Multivariate analysis identified extrathyroidal extension as the strongest prognostic factor for both RFS and DSS. Age >55 years and tumor size of ≥2 cm were also significant prognostic factors for DSS, while hereditary disease and lymph node metastasis were significant for RFS. Survival analysis after propensity-score matching of rearranged during transfection (RET)-negative and non-screened RET-positive groups showed comparable DSS but longer RFS in the RET-negative group.
Conclusion
Extrathyroidal extension was identified as the strongest prognostic factor for RFS and DSS. Older age and larger tumor size were associated with decreased DSS, while RET mutation and lymph node metastasis significantly impacted RFS.
7.Decline in sestrin 2 expression during aging shifts mesenchymal stem cell differentiation from osteogenic to adipogenic lineage
Do Yeun KIM ; Hyun-Jung PARK ; Jeong-Hwa BAEK
International Journal of Oral Biology 2024;49(3):69-78
Sestrin 2 (SESN2) is a member of the sestrin family of stress-induced proteins that negatively regulate agingassociated biological processes. This study aims to investigate the role of SESN2 in regulating the differentiation potential and senescence of mesenchymal stem cells (MSCs) derived from young and elderly donors. Bulk RNA sequencing revealed a common decline in the SESN2 mRNA levels in MSCs from elderly individuals, which was confirmed via reverse transcription-polymerase chain reaction and western blot analyses. SESN2 knockdown in MSCs from young donors resulted in phenotypic changes similar to those in MSCs from elderly donors, including an enhanced expression of senescence and adipogenic markers and diminished expression of osteogenic markers.To confirm the effect of decreased SESN2 expression on osteogenic and adipogenic differentiation, we induced Sesn2 knockdown in mouse bone marrow-derived MSCs. Sesn2 knockdown suppressed the mRNA expression of osteogenic marker genes, alkaline phosphatase activity, and matrix mineralization. Furthermore, Sesn2 knockdown enhanced mRNA expression of the adipogenic marker genes and intracellular lipid accumulation. These results suggest that a decline in SESN2 expression during aging contributes to the shift of MSC differentiation from osteogenic to adipogenic lineage.
8.Precision Oncology Clinical Trials: A Systematic Review of Phase II Clinical Trials with Biomarker-Driven, Adaptive Design
Hyerim HA ; Hee Yeon LEE ; Jee Hyun KIM ; Do Yeun KIM ; Ho Jung AN ; SeungJin BAE ; Hye-sung PARK ; Jin Hyoung KANG
Cancer Research and Treatment 2024;56(4):991-1013
Novel clinical trial designs are conducted in the precision medicine era. This study aimed to evaluate biomarker-driven, adaptive phase II trials in precision oncology, focusing on infrastructure, efficacy, and safety. We systematically reviewed and analyzed the target studies. EMBASE and PubMed searches from 2015 to 2023 generated 29 eligible trials. Data extraction included infrastructure, biomarker screening methodologies, efficacy, and safety profiles. Government agencies, cancer hospitals, and academic societies with accumulated experiences led investigator-initiated precision oncology clinical trials (IIPOCTs), which later guided sponsor-initiated precision oncology clinical trials (SIPOCTs). Most SIPOCTs were international studies with basket design. IIPOCTs primarily used the central laboratory for biomarker screening, but SIPOCTs used both central and local laboratories. Most of the studies adapted next-generation sequencing and/or immunohistochemistry for biomarker screening. Fifteen studies included an independent central review committee for outcome investigation. Efficacy assessments predominantly featured objective response rate as the primary endpoint, with varying results. Nine eligible studies contributed to the United States Food and Drug Administration’s marketing authorization. Safety monitoring was rigorous, but reporting formats lacked uniformity. Health-related quality of life and patient-reported outcomes were described in some protocols but rarely reported. Our results reveal that precision oncology trials with adaptive design rapidly and efficiently evaluate anticancer drugs’ efficacy and safety, particularly in specified biomarker-driven cohorts. The evolution from IIPOCT to SIPOCT has facilitated fast regulatory approval, providing valuable insights into the precision oncology landscape.
9.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.
10.2023 Revised Korean Thyroid Association Guidelines for the Diagnosis and Management of Thyroid Disease during Pregnancy and Postpartum
Ka Hee YI ; Hwa Young AHN ; Jin Hwa KIM ; So Young PARK ; Won Sang YOO ; Kyong Yeun JUNG ; Eun Kyung LEE ; Young Joo PARK ; Sun Wook KIM ; Chang Hoon YIM ; Yun Jae CHUNG ; Ho-Cheol KANG ; Do Joon PARK
International Journal of Thyroidology 2023;16(1):51-88
Thyroid hormone plays an important role in the process of implantation of a fertilized egg in the endometrium, as well as in the division and development of the fertilized egg. In addition, maternal thyroid hormone is essential for the formation and development of the fetal brain, nervous system, and bones. Therefore, when maternal thyroid hormone is insufficient, complications such as miscarriage, stillbirth, low birth weight and preeclampsia increase. Guidelines for the diagnosis and treatment of thyroid dysfunction during pregnancy were established and published by the American Endocrine Society, the American Thyroid Association, and the European Thyroid Society. The Korean Thyroid Society also published recommendations for diagnosis and treatment of thyroid disease during pregnancy and postpartum in 2014. However, since the revised guidelines of the American Thyroid Association were published in 2017, many studies, including large-scale randomized controlled trials, have been published in relation to thyroid and pregnancy, and the need to revise the existing recommendations has emerged in Korea.The main revisions of this recommendation are changes in the normal range of TSH during pregnancy, detailed description of treatment policies according to pregnant women’s autoantibodies and thyroid function status. Also, a description of the effect of thyroid autoantibodies on assisted reproductive procedures has been added.

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