12 results on '"Heechul Nam"'
Search Results
2. Diagnostic performance of serum exosomal miRNA-720 in hepatocellular carcinoma
- Author
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Jeong Won Jang, Ji Min Kim, Hye Seon Kim, Jin Seoub Kim, Ji Won Han, Soon Kyu Lee, Heechul Nam, Pil Soo Sung, Si Hyun Bae, Jong Young Choi, and Seung Kew Yoon
- Subjects
digestive system diseases - Abstract
Background/Aim: Hepatocellular carcinoma (HCC) is associated with poor prognosis, largely due to late detection. Highly accurate biomarkers are urgently needed to detect early-stage HCC. Our study aims to explore the diagnostic performance of serum exosomal microRNA (miR)-720 in HCC.Methods: Exosomal miRNA was measured via quantitative real-time PCR. A correlation analysis of exosomal miR-720 and tumor or clinico-demographic data of patients with HCC was performed. The receiver operating characteristic (ROC) curve was used to assess the diagnostic capacity of serum exosomal miR-720 for HCC, in comparison with α-fetoprotein (AFP) and prothrombin induced by vitamin K absence or antagonist-II (PIVKA-II).Results: MiR-720 was chosen as a potential HCC marker via miR microarray based on significant differential expression between tumor and non-tumor samples. Serum exosomal miR-720 was significantly upregulated in patients with HCC (n=114) versus other liver diseases (control, n=30), with a higher area under the ROC curve (AUC=0.931) than the other markers. Particularly, serum exosomal miR-720 showed superior performance in diagnosing small HCC (< 5 cm; AUC=0.930) compared with AFP (AUC=0.802) or PIVKA-II (AUC=0.718). Exosomal miR-720 levels showed marginal correlation with tumor size. The proportion of elevated miR-720 also increased with intrahepatic tumor stage progression. Unlike AFP or PIVKA-II showing a significant correlation with aminotransferase levels, the exosomal miR-720 level was not affected by aminotransferase levels.Conclusions: Serum exosomal miR-720 is an excellent biomarker for the diagnosis of HCC, with better performance than AFP or PIVKA-II. Its diagnostic utility is maintained even in small HCC and is unaffected by aminotransferase levels.
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- 2022
3. Case 9: A 62-Year-Old Woman With Jaundice and General Weakness
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Hee Sun Cho, Ji Won Han, Ji Hoon Kim, Heechul Nam, Pil Soo Sung, and Si Hyun Bae
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General Medicine - Published
- 2023
4. Tenofovir alafenamide alleviates nonalcoholic steatohepatitis in mice by blocking the phosphorylation of AKT in intrahepatic mononuclear phagocytes
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Pu Reun Roh, Sung Min Kim, Byung-Yoon Kang, Kyoung Do Mun, Jong Geun Park, Min Woo Kang, Wonhee Hur, Ji Won Han, Heechul Nam, Seung Kew Yoon, and Pil Soo Sung
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Pharmacology ,Lipopolysaccharides ,Mice ,Non-alcoholic Fatty Liver Disease ,Adenine ,Humans ,Animals ,General Medicine ,Phosphorylation ,Diet, High-Fat ,Proto-Oncogene Proteins c-akt ,Monocytes - Abstract
Although the prevalence of nonalcoholic steatohepatitis (NASH) is rapidly increasing, effective therapy is lacking. Tenofovir alafenamide (TAF) is a widely used antiviral drug for hepatitis B. In this study, we investigated the potential pharmacological effects of TAF on NASH.Two different NASH mouse models were established: 1) by subcutaneous injection of streptozotocin (0.2 mg) and feeding the mice a high-fat, high-cholesterol (HFHC) diet, and 2) feeding the mice a choline-deficient, L-amino acid-defined, high-fat (CDAHF) diet.Serum alanine aminotransferase and triglyceride levels in TAF-treated NASH mice were significantly lower than those in the mock-treated ones. The livers from the TAF-treated NASH mice showed attenuated mononuclear phagocyte (MP) infiltration compared to those from the mock-treated ones. TAF-treated NASH mice exhibited decreased liver infiltration of activated MPs (IAIETAF exerts anti-inflammatory effects in NASH livers by attenuating AKT phosphorylation in intrahepatic activated MPs. Therefore, TAF may serve as a new therapeutic option for NASH.
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- 2022
5. Persistence of intrahepatic hepatitis B virus DNA integration in patients developing hepatocellular carcinoma after hepatitis B surface antigen seroclearance
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Si Hyun Bae, Jin Seoub Kim, Seung Kew Yoon, Jeong Won Jang, Heechul Nam, Jong Young Choi, Kwon Yong Tak, Lewis R. Roberts, Hye Seon Kim, and Pil Soo Sung
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0301 basic medicine ,HBsAg ,Hepatitis B virus ,Carcinoma, Hepatocellular ,Population surveillance ,Virus integration ,medicine.disease_cause ,Hepatitis b surface antigen ,Persistence (computer science) ,03 medical and health sciences ,0302 clinical medicine ,Liver neoplasms ,Medicine ,Humans ,In patient ,lcsh:RC799-869 ,Molecular Biology ,Virus Integration ,Hepatitis B Surface Antigens ,Hepatology ,business.industry ,virus diseases ,DNA ,medicine.disease ,Hepatitis B ,Virology ,digestive system diseases ,030104 developmental biology ,Hepatocellular carcinoma ,030211 gastroenterology & hepatology ,lcsh:Diseases of the digestive system. Gastroenterology ,Original Article ,business ,Carcinogenesis - Abstract
Background/Aims: The role of hepatitis B virus (HBV) integration into the host genome in hepatocarcinogenesis following hepatitis B surface antigen (HBsAg) seroclearance remains unknown. Our study aimed to investigate and characterize HBV integration events in chronic hepatitis B (CHB) patients who developed hepatocellular carcinoma (HCC) after HBsAg seroclearance.Methods: Using probe-based HBV capturing followed by next-generation sequencing technology, HBV integration was examined in 10 samples (seven tumors and three non-tumor tissues) from seven chronic carriers who developed HCC after HBsAg loss. Genomic locations and patterns of HBV integration were investigated.Results: HBV integration was observed in six patients (85.7%) and eight (80.0%) of 10 tested samples. HBV integration breakpoints were detected in all of the non-tumor (3/3, 100%) and five of the seven (71.4%) tumor samples, with an average number of breakpoints of 4.00 and 2.43, respectively. Despite the lower total number of tumoral integration breakpoints, HBV integration sites in the tumors were more enriched within the genic area. In contrast, non-tumor tissues more often showed intergenic integration. Regarding functions of the affected genes, tumoral genes with HBV integration were mostly associated with carcinogenesis. At enrollment, patients who did not remain under regular HCC surveillance after HBsAg seroclearance had a large HCC, while those on regular surveillance had a small HCC.Conclusions: The biological functions of HBV integration are almost comparable between HBsAg-positive and HBsAgserocleared HCCs, with continuing pro-oncogenic effects of HBV integration. Thus, ongoing HCC surveillance and clinical management should continue even after HBsAg seroclearance in patients with CHB.
- Published
- 2020
6. Successful Sequential Therapy Involving Regorafenib after Failure of Sorafenib in a Patient with Recurrent Hepatocellular Carcinoma after Liver Transplantation
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Jong Young Choi, Soon Kyu Lee, Jeong Won Jang, Heechul Nam, Pil Soo Sung, Seung Kew Yoon, and Si Hyun Bae
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Oncology ,Sorafenib ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Liver transplantation ,medicine.disease ,digestive system diseases ,Recurrent Hepatocellular Carcinoma ,Metastasis ,Radiation therapy ,chemistry.chemical_compound ,chemistry ,Hepatocellular carcinoma ,Regorafenib ,Internal medicine ,medicine ,business ,Liver cancer ,neoplasms ,medicine.drug - Abstract
The efficacy and safety of sequential systemic therapy for the treatment of recurrent hepatocellular carcinoma (HCC) after liver transplantation (LT) are not well established. This study describes a successful experience where sequential therapy with sorafenib followed by regorafenib was used to treat recurrent HCC in a 54-year old male LT recipient. After HCC recurred in both lungs 10 months after LT, sorafenib was administered with radiation therapy to treat pulmonary metastases. However, after 4 months of sorafenib treatment showed progressive pulmonary metastases, sequential regorafenib treatment was started. After 3 months (cycles) of regorafenib treatment, tumor response was partial, and after 6 months (cycles), disease status remained stable without signs of progression or drug-related serious adverse events. This case suggests that sequential systemic therapy is feasible in patient with recurrent HCC after LT. (J Liver Cancer 2020;20:84-89)
- Published
- 2020
7. Real-life experience of ledipasvir and sofosbuvir for HCV infected Korean patients: a multicenter cohort study
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Soon Kyu Lee, Sung Won Lee, Hae Lim Lee, Hee Yeon Kim, Chang Wook Kim, Do Seon Song, U Im Chang, Jin Mo Yang, Sun Hong Yoo, Jung Hyun Kwon, Soon Woo Nam, Seok-Hwan Kim, Myeong Jun Song, Jaejun Lee, Hyun Yang, Si Hyun Bae, Ji Won Han, Heechul Nam, Pil Soo Sung, Jeong Won Jang, Jong Young Choi, and Seung Kew Yoon
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Liver Cirrhosis ,Cohort Studies ,Treatment Outcome ,Genotype ,Republic of Korea ,Humans ,RNA ,Hepacivirus ,Sofosbuvir ,Hepatitis C, Chronic ,Antiviral Agents ,Hepatitis C - Abstract
Background/Aims: To evaluate the efficacy and safety of ledipasvir/sofosbuvir (LDV/SOF) therapy in hepatitis C virus (HCV)-infected Korean patients in a real clinical setting.Methods: A total of 273 patients who received LDV/SOF therapy between May 2016 and February 2021 were consecutively enrolled and analyzed. A per-protocol analysis was performed to evaluate the virologic response.Results: Seventy-five percent were infected with genotype 1, and 25% were infected with genotype 2. A hundred eightyone (66.3%) patients had chronic hepatitis, 74 (27.1%) had compensated cirrhosis, eight (2.9%) had decompensated cirrhosis, and 10 (3.7%) had undergone liver transplantation. Undetectable HCV RNA at week 4 was achieved in 90.2% (231/256) of patients, 99.2% (250/252) achieved the end of treatment response, and 98.1% (202/206) achieved sustained virologic response at 12 weeks post-treatment (SVR12). According to liver function, the SVR12 rates were 99.3% (135/136) in chronic hepatitis, 96.4% (53/55) in compensated cirrhosis, and 100% (6/6) in decompensated cirrhosis. The SVR12 rates according to the genotype were 98.2% (167/170) for genotype 1 and 97.2% (35/36) for genotype 2. An 8-week LDV/SOF treatment in treatment-naïve chronic hepatitis patients with HCV RNA < 6,000,000 IU/mL at baseline resulted in 100% (23/23) SVR12 rates. Overall, LDV/SOF was tolerated well, with a 0.7% (2/273) discontinuation rate due to adverse events that were unrelated to LDV/SOF.Conclusions: LDV/SOF is effective and safe for treating HCV-infected Korean patients with high SVR12 rates.
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- 2022
8. Exosomal miR-125b Exerts Anti-Metastatic Properties and Predicts Early Metastasis of Hepatocellular Carcinoma
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Hye Seon Kim, Jin Seoub Kim, Na Ri Park, Heechul Nam, Pil Soo Sung, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon, Wonhee Hur, and Jeong Won Jang
- Subjects
0301 basic medicine ,Cancer Research ,Cell signaling ,Exosome ,Metastasis ,miR-125b ,03 medical and health sciences ,0302 clinical medicine ,microRNA ,medicine ,exosome ,metastasis ,Epithelial–mesenchymal transition ,RC254-282 ,Original Research ,business.industry ,Cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,hepatocellular carcinoma ,medicine.disease ,Reverse transcription polymerase chain reaction ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Cancer research ,biomarker ,business ,epithelial – mesenchymal – transition - Abstract
Background & AimsCancer metastasis is responsible for the majority of cancer-related deaths. Exosomal miRNAs have emerged as promising biomarkers for cancer, serving as signaling molecules that can regulate tumor growth and metastasis. This study examined circulating exosomal miRNAs that could predict hepatocellular carcinoma (HCC) metastasis.MethodsExosomal miRNA was measured by quantitative real-time PCR (qRT-PCR) in a large set of patients (n = 284). To investigate the role of exosomal miRNA in HCC, we performed a series of in vitro tests, such as exosome labeling, qRT-PCR, reverse transcription PCR, wound healing assay, transwell assay, and Western blot assay.ResultsExosomal miR-125b was drastically downregulated in HCC patients with metastasis than in those without metastasis. In vitro, we observed the uptake of miR-125b by exosome in recipient cells. Exosome-mediated miR-125b significantly inhibited migration and invasion abilities and downregulated the mRNA expressions of MMP-2, MMP-9, and MMP-14 in recipient cells via intercellular communication. Further investigation revealed that miR-125b suppressed SMAD2 protein expression in recipient cells by binding to its 3′ untranslated regions. Exosome-mediated miR-125b transfer also disrupted TGF-β1–induced epithelial–mesenchymal transition and TGF-β1/SMAD signaling pathway in recipient cells by leading to a decrease of SMAD2 protein expression. Moreover, exosomal miR-125b was downregulated after metastasis compared with that at baseline in patients with serial measurements before and after metastasis.ConclusionsThe results imply that exosome-mediated miR-125b exerts anti-metastatic properties in HCC. These findings highlight that circulating exosomal miR-125b might represent a reliable biomarker with diagnostic and therapeutic implications for extrahepatic metastasis from HCC.
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- 2021
9. Reactivation of Resolved Hepatitis B After Daratumumab for Multiple Myeloma
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Chang-Ki Min, Jeong Won Jang, Soon Kyu Lee, Pil Soo Sung, Sung-Soo Park, Jong Young Choi, Seung Kew Yoon, and Heechul Nam
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Microbiology (medical) ,Hepatitis B virus ,HBsAg ,Hepatitis B Surface Antigens ,business.industry ,Liver failure ,Daratumumab ,Antibodies, Monoclonal ,Hepatitis B ,medicine.disease ,medicine.disease_cause ,Hepatitis b surface antigen ,Virology ,Infectious Diseases ,medicine ,Humans ,Virus Activation ,Hepatitis B Antibodies ,business ,Multiple Myeloma ,Multiple myeloma - Abstract
The risk of reactivation of resolved hepatitis B virus (HBV) in hepatitis B surface antigen (HBsAg)-negative multiple myeloma patients after daratumumab has not been reported. Among 93 patients with daratumumab treatment, reactivation occurred in 6 patients (6.5%) with one hepatic failure. This is the first report demonstrating a considerable risk of reactivation of resolved HBV after daratumumab.
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- 2021
10. Tenofovir disoproxil fumarate directly ameliorates liver fibrosis by inducing hepatic stellate cell apoptosis via downregulation of PI3K/Akt/mTOR signaling pathway
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Sung Won Lee, Sung Min Kim, Wonhee Hur, Byung-Yoon Kang, Hae Lim Lee, Heechul Nam, Sun Hong Yoo, Pil Soo Sung, Jung Hyun Kwon, Jeong Won Jang, Seong-Jun Kim, and Seung Kew Yoon
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Liver Cirrhosis ,Male ,Apoptosis ,Thioacetamide ,Biochemistry ,Mice ,Phosphatidylinositol 3-Kinases ,Animal Cells ,Medicine and Health Sciences ,Public and Occupational Health ,Multidisciplinary ,Cell Death ,Liver Diseases ,TOR Serine-Threonine Kinases ,Animal Models ,Vaccination and Immunization ,Experimental Organism Systems ,Liver ,Cell Processes ,Liver Fibrosis ,Medicine ,Cellular Types ,Anatomy ,Research Article ,Autophagic Cell Death ,Science ,Immunology ,Mouse Models ,Gastroenterology and Hepatology ,Research and Analysis Methods ,Antiviral Agents ,Model Organisms ,Antiviral Therapy ,Hepatic Stellate Cells ,Animals ,Humans ,Tenofovir ,Biology and Life Sciences ,Proteins ,Cell Biology ,Fibrosis ,Mice, Inbred C57BL ,Gene Expression Regulation ,Animal Studies ,Hepatocytes ,Preventive Medicine ,Collagens ,Proto-Oncogene Proteins c-akt ,Developmental Biology - Abstract
Background Antifibrotic agent for the treatment of liver fibrosis has not been developed so far. Long term treatment of chronic hepatitis B patients with antiviral drugs tenofovir disoproxil fumarate (TDF) and entecavir (ETV) results in the regression of liver fibrosis, but the underlying mechanism has not been clarified. Therefore, we aimed to investigate the direct impact of TDF and ETV on liver fibrosis. Methods Activated hepatic stellate cell (HSC) cell lines were used to evaluate the effects of TDF and ETV. After treatment with each antiviral agent, cell viability, morphology, apoptotic features, autophagy and antifibrosis signalling pathways were examined. Then, collagen deposition, fibrosis markers and activated HSCs were measured in liver tissues of the liver fibrosis model mice. Results After TDF treatment, the viabilities of LX2 and HSC-T6 cells were decreased, and the cells exhibited apoptotic features, but ETV did not induce these effects. Cleavage of PARP and Caspase-3 and the inhibition of the antiapoptotic gene Bcl-xl indicated activated HSC apoptosis following TDF treatment. TDF simultaneously increased autophagy, which also regulated apoptosis through crosstalk. TDF inactivated the PI3K/Akt/mTOR signalling pathway, which was associated with the activation of both apoptosis and autophagy. In the liver fibrosis mouse model, the fibrotic area and activated HSC markers were decreased by TDF but not ETV treatment. Additionally, apoptotic cells were concentrated in the periportal fibrotic area after TDF treatment, which indicated the specific antifibrotic effect of TDF. Conclusions TDF directly ameliorates liver fibrosis by downregulating the PI3K/Akt/mTOR signalling pathway, which results in the apoptosis of activated HSCs. The antifibrotic effects of TDF indicate that it may be a therapeutic agent for the treatment of liver fibrosis.
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- 2021
11. Significance of TERT Genetic Alterations and Telomere Length in Hepatocellular Carcinoma
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Changmin Kim, Hye Seon Kim, Seung Kew Yoon, Jeong-Won Jang, Si-Hyun Bae, Jin Young Park, Kwon-Yong Tak, Jong-Young Choi, Soon-Kyu Lee, Heechul Nam, Pil-Soo Sung, and Jin-Seoub Kim
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telomere ,Cancer Research ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,biomarkers ,AKT1 ,HCCS ,Biology ,medicine.disease ,Telomere ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Gene expression ,liver neoplasm ,treatment outcome ,medicine ,Cancer research ,030211 gastroenterology & hepatology ,Liver neoplasm ,Telomerase reverse transcriptase ,Gene ,RC254-282 ,TERT - Abstract
Telomerase reverse transcriptase (TERT) mutations are reportedly the most frequent somatic genetic alterations in hepatocellular carcinoma (HCC). An integrative analysis of TERT-telomere signaling during hepatocarcinogenesis is lacking. This study aimed to investigate the clinicopathological association and prognostic value of TERT gene alterations and telomere length in HCC patients undergoing hepatectomy as well as transarterial chemotherapy (TACE). TERT promoter mutation, expression, and telomere length were analyzed by Sanger sequencing and real-time PCR in 305 tissue samples. Protein–protein interaction (PPI) analysis was performed to identify a set of genes that physically interact with TERT. The PPI analysis identified eight key TERT-interacting genes, namely CCT5, TUBA1B, mTOR, RPS6KB1, AKT1, WHAZ, YWHAQ, and TERT. Among these, TERT was the most strongly differentially expressed gene. TERT promoter mutations were more frequent, TERT expression was significantly higher, and telomere length was longer in tumors versus non-tumors. TERT promoter mutations were most frequent in HCV-related HCCs and less frequent in HBV-related HCCs. TERT promoter mutations were associated with higher TERT levels and longer telomere length and were an independent predictor of worse overall survival after hepatectomy. TERT expression was positively correlated with tumor differentiation and stage progression, and independently predicted shorter time to progression after TACE. The TERT-telomere network may have a crucial role in the development and progression of HCC. TERT-telomere abnormalities might serve as useful biomarkers for HCC, but the prognostic values may differ with tumor characteristics and treatment.
- Published
- 2021
12. Partial Anomalous Pulmonary Venous Return (PAPVR) in a Patient with Sjogren's Syndrome
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Hae-Min Lee, Jennifer Lee, Heechul Nam, Sung-Hwan Park, Seung-Ki Kwok, Kyung-Su Park, Ho-Youn Kim, Honk-Ki Min, and Keun-Suk Yang
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medicine.medical_specialty ,Exacerbation ,business.industry ,Interstitial lung disease ,Partial anomalous pulmonary venous return ,medicine.disease ,Pulmonary hypertension ,respiratory tract diseases ,Shunt (medical) ,Rheumatology ,Internal medicine ,Anomalous pulmonary vein ,Cardiology ,Medicine ,In patient ,Sjogren s ,business - Abstract
Pulmonary hypertension (PH) is a rare manifestation in patients with primary Sjogren’s syndrome (pSS) and it can occur with or without interstitial lung disease (ILD). Patients with PH and ILD who show signs of exacerbation of dyspnea are commonly assessed for pure PH aggravation, ILD progression or pulmonary infection. However, the presence of congenital cardiac anomalies, such as partial anomalous pulmonary vein return (PAPVR), can also be a cause of dyspnea exacerbation. PAPVR is a rare congenital anomaly that involves drainage of 1 to 3 pulmonary veins into the right-sided heart circulation, resulting in a partial left-to-right shunt. Here we present a case of PAPVR as the cause of PH aggravation in a patient with pSS with accompanying PH.
- Published
- 2013
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