2.Robinetin Alleviates Metabolic Failure in Liver through Suppression of p300–CD38 Axis
Ji-Hye SONG ; Hyo-Jin KIM ; Jangho LEE ; Seung-Pyo HONG ; Min-Yu CHUNG ; Yu-Geun LEE ; Jae Ho PARK ; Hyo-Kyoung CHOI ; Jin-Taek HWANG
Biomolecules & Therapeutics 2024;32(2):214-223
Metabolic abnormalities in the liver are closely associated with diverse metabolic diseases such as non-alcoholic fatty liver disease, type 2 diabetes, and obesity. The aim of this study was to evaluate the ameliorating effect of robinetin (RBN) on the significant pathogenic features of metabolic failure in the liver and to identify the underlying molecular mechanism. RBN significantly decreased triglyceride (TG) accumulation by downregulating lipogenesis-related transcription factors in AML-12 murine hepatocyte cell line. In addition, mice fed with Western diet (WD) containing 0.025% or 0.05% RBN showed reduced liver mass and lipid droplet size, as well as improved plasma insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) values.CD38 was identified as a target of RBN using the BioAssay database, and its expression was increased in OPA-treated AML-12 cells and liver tissues of WD-fed mice. Furthermore, RBN elicited these effects through its anti-histone acetyltransferase (HAT) activity. Computational simulation revealed that RBN can dock into the HAT domain pocket of p300, a histone acetyltransferase, which leads to the abrogation of its catalytic activity. Additionally, knock-down of p300 using siRNA reduced CD38 expression.The chromatin immunoprecipitation (ChIP) assay showed that p300 occupancy on the promoter region of CD38 was significantly decreased, and H3K9 acetylation levels were diminished in lipid-accumulated AML-12 cells treated with RBN. RBN improves the pathogenic features of metabolic failure by suppressing the p300–CD38 axis through its anti-HAT activity, which suggests that RBN can be used as a new phytoceutical candidate for preventing or improving this condition.
3.Longitudinal Comparative Analysis of Circulating Tumor DNA and Matched Tumor Tissue DNA in Patients with Metastatic Colorectal Cancer Receiving Palliative First-Line Systemic Anti-Cancer Therapy
Seung-been LEE ; Ji-Won KIM ; Hong-Geun KIM ; Sung-Hyun HWANG ; Kui-Jin KIM ; Ju Hyun LEE ; Jeongmin SEO ; Minsu KANG ; Eun Hee JUNG ; Koung Jin SUH ; Se Hyun KIM ; Jin Won KIM ; Yu Jung KIM ; Jee Hyun KIM ; Nak-Jung KWON ; Keun-Wook LEE
Cancer Research and Treatment 2024;56(4):1171-1182
Purpose:
This study aimed to compare tumor tissue DNA (ttDNA) and circulating tumor DNA (ctDNA) to explore the clinical applicability of ctDNA and to better understand clonal evolution in patients with metastatic colorectal cancer undergoing palliative first-line systemic therapy.
Materials and Methods:
We performed targeted sequencing analysis of 88 cancer-associated genes using germline DNA, ctDNA at baseline (baseline-ctDNA), and ctDNA at progressive disease (PD-ctDNA). The results were compared with ttDNA data.
Results:
Among 208 consecutively enrolled patients, we selected 84 (41 males; median age, 59 years; range, 35 to 90 years) with all four sample types available. A total of 202 driver mutations were found in 34 genes. ttDNA exhibited the highest mutation frequency (n=232), followed by baseline-ctDNA (n=155) and PD-ctDNA (n=117). Sequencing ctDNA alongside ttDNA revealed additional mutations in 40 patients (47.6%). PD-ctDNA detected 13 novel mutations in 10 patients (11.9%) compared to ttDNA and baseline-ctDNA. Notably, seven mutations in five patients (6.0%) were missense or nonsense mutations in APC, TP53, SMAD4, and CDH1 genes. In baseline-ctDNA, higher maximal variant allele frequency (VAF) values (p=0.010) and higher VAF values of APC (p=0.012), TP53 (p=0.012), and KRAS (p=0.005) mutations were significantly associated with worse overall survival.
Conclusion
While ttDNA remains more sensitive than ctDNA, our ctDNA platform demonstrated validity and potential value when ttDNA was unavailable. Post-treatment analysis of PD-ctDNA unveiled new pathogenic mutations, signifying cancer’s clonal evolution. Additionally, baseline-ctDNA’s VAF values were prognostic after treatment.
4.Effective Endoscopic Submucosal Dissection of a Huge Esophageal Liposarcoma: A Case Report
Myeong Jin LEE ; Moon Won LEE ; Dong Chan JOO ; Seung Min HONG ; Dong Hoon BAEK ; Bong Eun LEE ; Gwang Ha KIM ; Geun Am SONG
The Korean Journal of Gastroenterology 2024;83(6):243-246
This case report presents the successful endoscopic submucosal dissection (ESD) of a well-differentiated esophageal liposarcoma in a 51-year-old male with persistent dysphagia. The cause was initially diagnosed as a 10 cm pedunculated lesion extending from the upper esophageal sphincter to the mid-esophagus. An ESD was chosen over traditional surgery because it is less invasive. The procedure involved a precise submucosal injection and excision with special techniques to manage bleeding from a central vessel.Despite the extraction challenges owing to the size of the lesion, it was successfully removed orally. A histopathological examination of the 8.3×4.2×2.3 cm specimen revealed the characteristic features of a well-differentiated liposarcoma, including MDM2 and CDK4 positivity. The follow-up revealed no recurrence, and active surveillance has been performed since. This report highlights the versatility of ESD in treating significant esophageal tumors and provides evidence for its efficacy as a minimally invasive alternative.
6.Effect of abatacept versus csDMARDs on rheumatoid arthritis-associated interstitial lung disease
Kyung-Ann LEE ; Bo Young KIM ; Sung Soo KIM ; Yun Hong CHEON ; Sang-Il LEE ; Sang-Hyon KIM ; Jae Hyun JUNG ; Geun-Tae KIM ; Jin-Wuk HUR ; Myeung-Su LEE ; Yun Sung KIM ; Seung-Jae HONG ; Suyeon PARK ; Hyun-Sook KIM
The Korean Journal of Internal Medicine 2024;39(5):855-864
Background/Aims:
To compare the effects of abatacept and conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) on the progression and development of rheumatoid arthritis-associated interstitial lung disease (RA-ILD).
Methods:
This multi-center retrospective study included RA patients receiving abatacept or csDMARDs who underwent at least two pulmonary function tests and/or chest high-resolution computed tomography (HRCT). We compared the following outcomes between the groups: progression of RA-ILD, development of new ILD in RA patients without ILD at baseline, 28-joint Disease Activity Score with the erythrocyte sedimentation rate (DAS28-ESR), and safety. Longitudinal changes were compared between the groups by using a generalized estimating equation.
Results:
The study included 123 patients who were treated with abatacept (n = 59) or csDMARDs (n = 64). Nineteen (32.2%) and 38 (59.4%) patients treated with abatacept and csDMARDs, respectively, presented with RA-ILD at baseline. Newly developed ILD occurred in one patient receiving triple csDMARDs for 32 months. Among patients with RA-ILD at baseline, ILD progressed in 21.1% of cases treated with abatacept and 34.2% of cases treated with csDMARDs during a median 21-month follow-up. Longitudinal changes in forced vital capacity and diffusing capacity for carbon monoxide were comparable between the two groups. However, the abatacept group showed a more significant decrease in DAS28-ESR and glucocorticoid doses than csDMARDs group during the follow-up. The safety of both regimens was comparable.
Conclusions
Abatacept and csDMARDs showed comparable effects on the development and stabilization of RA-ILD. Nevertheless, compared to csDMARDs, abatacept demonstrated a significant improvement in disease activity and led to reduced glucocorticoid use.
7.The Role of Adjuvant Therapy Following Surgical Resection of Small Cell Lung Cancer: A Multi-Center Study
Seong Yong PARK ; Samina PARK ; Geun Dong LEE ; Hong Kwan KIM ; Sehoon CHOI ; Hyeong Ryul KIM ; Yong-Hee KIM ; Dong Kwan KIM ; Seung-Il PARK ; Tae Hee HONG ; Yong Soo CHOI ; Jhingook KIM ; Jong Ho CHO ; Young Mog SHIM ; Jae Ill ZO ; Kwon Joong NA ; In Kyu PARK ; Chang Hyun KANG ; Young-Tae KIM ; Byung Jo PARK ; Chang Young LEE ; Jin Gu LEE ; Dae Joon KIM ; Hyo Chae PAIK
Cancer Research and Treatment 2023;55(1):94-102
Purpose:
This multi-center, retrospective study was conducted to evaluate the long-term survival in patients who underwent surgical resection for small cell lung cancer (SCLC) and to identify the benefit of adjuvant therapy following surgery.
Materials and Methods:
The data of 213 patients who underwent surgical resection for SCLC at four institutions were retrospectively reviewed. Patients who received neoadjuvant therapy or an incomplete resection were excluded.
Results:
The mean patient age was 65.29±8.93 years, and 184 patients (86.4%) were male. Lobectomies and pneumonectomies were performed in 173 patients (81.2%), and 198 (93%) underwent systematic mediastinal lymph node dissections. Overall, 170 patients (79.8%) underwent adjuvant chemotherapy, 42 (19.7%) underwent radiotherapy to the mediastinum, and 23 (10.8%) underwent prophylactic cranial irradiation. The median follow-up period was 31.08 months (interquartile range, 13.79 to 64.52 months). The 5-year overall survival (OS) and disease-free survival were 53.4% and 46.9%, respectively. The 5-year OS significantly improved after adjuvant chemotherapy in all patients (57.4% vs. 40.3%, p=0.007), and the survival benefit of adjuvant chemotherapy was significant in patients with negative node pathology (70.8% vs. 39.7%, p=0.004). Adjuvant radiotherapy did not affect the 5-year OS (54.6% vs. 48.5%, p=0.458). Age (hazard ratio [HR], 1.032; p=0.017), node metastasis (HR, 2.190; p < 0.001), and adjuvant chemotherapy (HR, 0.558; p=0.019) were associated with OS.
Conclusion
Adjuvant chemotherapy after surgical resection in patients with SCLC improved the OS, though adjuvant radiotherapy to the mediastinum did not improve the survival or decrease the locoregional recurrence rate.
8.Guideline for the Surgical Management of Locally Invasive Differentiated Thyroid Cancer From the Korean Society of Head and Neck Surgery
Jun-Ook PARK ; Joo Hyun KIM ; Young Hoon JOO ; Sang-Yeon KIM ; Geun-Jeon KIM ; Hyun Bum KIM ; Dong-Hyun LEE ; Hyun Jun HONG ; Young Min PARK ; Eun-Jae CHUNG ; Yong Bae JI ; Kyoung Ho OH ; Hyoung Shin LEE ; Dong Kun LEE ; Ki Nam PARK ; Myung Jin BAN ; Bo Hae KIM ; Do Hun KIM ; Jae-Keun CHO ; Dong Bin AHN ; Min-Su KIM ; Jun Girl SEOK ; Jeon Yeob JANG ; Hyo Geun CHOI ; Hee Jin KIM ; Sung Joon PARK ; Eun Kyung JUNG ; Yeon Soo KIM ; Yong Tae HONG ; Young Chan LEE ; Ho-Ryun WON ; Sung-Chan SHIN ; Seung-Kuk BAEK ; Soon Young KWON
Clinical and Experimental Otorhinolaryngology 2023;16(1):1-19
The aim of this study was to develop evidence-based recommendations for determining the surgical extent in patients with locally invasive differentiated thyroid cancer (DTC). Locally invasive DTC with gross extrathyroidal extension invading surrounding anatomical structures may lead to several functional deficits and poor oncological outcomes. At present, the optimal extent of surgery in locally invasive DTC remains a matter of debate, and there are no adequate guidelines. On October 8, 2021, four experts searched the PubMed, Embase, and Cochrane Library databases; the identified papers were reviewed by 39 experts in thyroid and head and neck surgery. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of evidence, and to develop and report recommendations. The strength of a recommendation reflects the confidence of a guideline panel that the desirable effects of an intervention outweigh any undesirable effects, across all patients for whom the recommendation is applicable. After completing the draft guidelines, Delphi questionnaires were completed by members of the Korean Society of Head and Neck Surgery. Twenty-seven evidence-based recommendations were made for several factors, including the preoperative workup; surgical extent of thyroidectomy; surgery for cancer invading the strap muscles, recurrent laryngeal nerve, laryngeal framework, trachea, or esophagus; and surgery for patients with central and lateral cervical lymph node involvement. Evidence-based guidelines were devised to help clinicians make safer and more efficient clinical decisions for the optimal surgical treatment of patients with locally invasive DTC.
9.Survey results from the participants of the Asian Young Endoscopist Award and International Young Endoscopist Award as part of the International Digestive Endoscopy Network
Tae-Geun GWEON ; Sang Hoon KIM ; Ki Bae BANG ; Seung Wook HONG ; Won Jae YOON ; Sung Noh HONG ; Jae Jun PARK ; Jimin HAN ; Ja Seol KOO ; Oh Young LEE ;
Clinical Endoscopy 2023;56(5):674-676
10.A Gastric Magnetic Foreign Body Incidentally Detected Several Years after Ingestion
Dong Chan JOO ; Moon Won LEE ; Seung Min HONG ; Dong Hoon BAEK ; Bong Eun LEE ; Gwang Ha KIM ; Geun Am SONG
The Korean Journal of Gastroenterology 2023;82(4):198-201
Foreign body ingestion is commonly seen in children. However, occasionally it may also be seen among adults and is often associated with intellectual disability, psychiatric disorders, and alcoholism. Ingestion of a magnetic foreign body may cause complications such as gastrointestinal tract perforation, wherein emergency endoscopic removal of the foreign body is generally required. Here, we report a rare case of a 59-year-old male with an intellectual disability and psychiatric disorder in whom metallic objects in the stomach cavity were accidentally discovered during abdominal CT. Esophagogastroduodenoscopy revealed several metallic objects attached to two magnets, which had been ingested several years before and had remained in the stomach cavity. The magnets and metallic objects were safely removed endoscopically using rat-tooth forceps without complications.

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