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( Hyun Su Baek ),( Hye Sung Lee ),( Bok Joo Kim ),( In Kyo Chung ),( Chul Hoon Kim ),( Sun Mi Jin ),( Hie Sung Hwang ),( Sang Hun Shin2 ) 한국조직공학·재생의학회 2011 조직공학과 재생의학 Vol.8 No.6
The objective of this study was to evaluate platelet-rich fibrin (PRF)’s effectiveness in repairing articular disc defect in the temporomandibular joint (TMJ) of rabbits. Eight rabbits were divided into four groups of two rabbits each, corresponding to groups A, B, C, and D. Both TMJs of all of the rabbits were used in the experiments: the right joints comprised the experimental groups, and the left ones, the control groups. The disc defect was circular and 2 mm in diameter. In the experimental groups, the PRF was compressed into the defect, whereas the control group defects were left untreated. A, B, C, and D groups were sacrificed at the 1st, 2nd, 4th and 6th weeks, respectively. The defects of each control group exhibited no specific changes. Contrastingly, in each experimental group, there was an increased number of chondroblasts at the margins of the defects, along with accelerated cell differentiation and a columnar cell arrangement observable at the time of cell differentiation. The experimental groups showed inflammatory cell infiltrations and fibrosis by the 1st week, maturation of chondrocytes by the 2nd week, and proliferation by the 4th week, after which the defects began to be filled with chondrocytes, a process that was complete after the 6th week. In the histological evaluation (H-E), the experimental groups showed significant increases of chondroblasts after the 2nd and 4th weeks, as well as regular columns of chondrocyte arrays observable during cell division. After 6 weeks, the defects were filled with chondrocytes.
( Shin Hwang ),( Su-min Ha ),( Chul-soo Ahn ),( Ki-hun Kim ),( Deok-bog Moon ),( Tae-yong Ha ),( Gi-won Song ),( Dong-hwan Jung ),( Gil-chun Park ),( Hwi-dong Cho ),( Jae-hyun Kwon ),( Sang-hyun Kang 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1
Aims: This study aimed to assess patterns of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) and to establish long-term surveillance protocols for late HCC recurrence. Methods: The 232 LT recipients experiencing subsequent HCC recurrence were categorized as Group 1, early recurrence (within 1 year of LT; n=117); Group 2, late recurrence (occurring in years 2-5; n=93); and Group 3, very late recurrence (after year 5; n=22). Results: Recurrence was detected by only elevated tumor marker levels in 11.1%, 30.1%, and 45.5% of patients in Groups 1, 2, and 3, respectively (P<0.001). The proportion of intrahepatic and extrahepatic metastases was similar in all three groups. Common sites of extrahepatic metastasis were the lung and bone; these were also similar across the three groups. Overall post-recurrence patient survival rates were 60.2% at 1 year, 28.2% at 3 years, 20.5% at 5 years, and 7.0% at 10 years. Median post-recurrence survival periods were 10.2, 23.8, and 37.0 months in Groups 1, 2, and 3, respectively. Conclusions: While the pattern of HCC recurrence was similar regardless of time of recurrence, post-recurrence survival was significantly longer in patients with later recurrence. Long-term surveillance for HCC recurrence beyond 5 years post-LT is recommended.
( Shin Hwang ),( Hee-jung Wang ),( Jae-won Joh ),( Dong-goo Kim ),( Kyung Sik Kim ),( Kyung-suk Suh ),( Seong Hoon Kim ),( Hee-chul Yu ),( Chol-kyoon Cho ),( Ki-hun Kim ),( Young-joo Lee ),( Sung-gyu 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1
Aims: We previously demonstrated that multiplication of α-fetoprotein (AFP), des-γ-carboxy prothrombin (DCP) and tumor volume (TV) (ADV score, expressed in log10) is an integrated surrogate marker of post-resection prognosis for hepatocellular carcinoma (HCC). Positron emission tomography (PET) reflects the tumor biology. We intended to assess whether preoperative ADV score combined with PET finding can predict the prognosis for large HCC. Methods: Nine institutions participated in this study supported by KASL research fund. Selection criteria were preoperative measurement of AFP and DCP, FDG-PET and macroscopic curative resection of solitary HCC ≥8 cm, by which 526 patients who underwent surgery between 2008 and 2014 were selected. Results: Median values were 11.0 cm for tumor diameter, 402 mL for tumor volume, and 8.3 for ADV score. Expression levels of AFP and DCP were not correlated (r<sup>2</sup>=0.02, p=0.002). Tumor recurrence and patient survival were significantly different according to ADV score cutoffs of 6 and 9 (p=0.000) and PET findings (p=0.000). Both ADV score cutoff at 6 and hypermetabolic PET were independent risk factors for tumor recurrence (HR 1.9 and 1.8) and patient survival (HR 2.3 and 3.0), respectively. Combination of ADV score cutoff at 6 and PET (ADV6-PET) resulted in great prognostic contrasts in tumor recurrence and patient survival (Fig. 1; all p=0.000). After exclusion of preoperative treatment cases, such prognostic contrast was further enhanced. Independent risk factors for tumor recurrence and patient survival were ADV6-PET (HR 1.6 and 2.7), microvascular invasion (HR 1.7 and 1.9), macrovascular invasion (HR 1.5 and 1.5) and satellite nodule (HR 1.5 and 2.0), respectively. Conclusions: The prognostic power of ADV6-PET was quite comparable to that of well-known pathological risk factors, thus that it can be used to predict the post-resection outcomes during preoperative planning for resection of large HCC.
( Shin Hwang ),( Ki-hun Kim ),( Young-joo Lee ),( Gi-won Song ),( Deok-bog Moon ),( Tae-yong Ha ),( Dong-hwan Jung ),( Sung-gyu Lee ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1
Aims: We previously demonstrated that multiplication of α-fetoprotein (AFP), des-γ-carboxy prothrombin (DCP) and tumor volume (TV) (ADV score, expressed in log10) is an integrated surrogate marker of post-resection prognosis for hepatocellular carcinoma (HCC). We hypothesized that aggressive tumor biology is associated with wider tumor spread, thus requiring systematic resection (SR) than non-systematic resection (NSR). We intended to assess the prognostic benefit of SR according to ADV score. Methods: Patient selection conditions were curative resection for solitary HCC of 2.0~5.0 cm and preoperative measurement of AFP and DCP. During 9-year study period from 2006 to 2014, 1577 patients were select. Results: Preoperative patient profiles were not statistically different between SR and NSR groups. Cumulative tumor recurrence and overall patient rates were better in SR group than in NSR group (all p=0.000). When confining to patients with ADV < 4, SR group showed lower recurrence and higher survival than NSR group (all p≤0.010; Fig. 1A). In contrast, when confining to patients with ADV ≥4, SR group did not show significant difference in recurrence and survival comparing with NSR group (all p≥0.092; Fig. 1B). SR group showed lower recurrence and higher survival than NSR group in patients with no microvascular invasion (all p=0.000), but such prognostic benefit was no longer valid in patients with microvascular invasion (all p≥0.156). Independent risk factors for tumor recurrence and patient survival were microvascular invasion, NSR and ADV score >4. Conclusions: Unlike our hypothesis, our results demonstrated that the prognostic benefit from SR was evident only in patients with ADV <4 or absence of microvascular invasion. Thus, patients with less aggressive tumor biology such as small HCC with low expression of tumor markers are more benefited from SR. Therefore, SR for HCC is highly recommended to all HCC patients regardless of tumor size and expression status of tumor markers.
Stimulation of Innate Immune Function by <i>Panax ginseng</i> after Heat Processing
Shin, Myoung-Sook,Song, Ji Hoon,Choi, Pilju,Lee, Jong Hun,Kim, Song-Yi,Shin, Kwang-Soon,Ham, Jungyeob,Kang, Ki Sung American Chemical Society 2018 Journal of agricultural and food chemistry Vol.66 No.18
<P><I>Panax ginseng</I> Meyer has been used for the treatment of immune diseases and for strengthening the immune function. In this study, we evaluated the innate immune-stimulating functions and action mechanisms of white ginseng (WG) and heat-processed ginseng (HPG) in RAW264.7 cells. According to LC-MS analysis results, WG contained typical ginsenosides, such as Rb1, Rc, Rb2, Rd, and Rg1, whereas HPG contained Rg3, Rk1, and Rg5 as well as typical ginsenosides. HPG, not WG, enhanced NF-κB transcriptional activity, cytokine production (IL-6 and TNF-α), and MHC class I and II expression in RAW264.7 cells. In addition, HPG phosphorylated MAPKs and NF-kB pathways. In experiments with inhibitors, the ERK inhibitor completely suppressed the effect of HPG on IL-6 and TNF-α production. HPG-induced c-Jun activation was suppressed by an ERK inhibitor and partially suppressed by JNK, p38, and IκBα inhibitors. Collectively, these results suggested that HPG containing Rg3, Rg5, and Rk1 increased macrophage activation which was regulated by the ERK/c-Jun pathway in RAW264.7 cells.</P> [FIG OMISSION]</BR>
( Shin Hwang ),( Woo-hyoung Kang ),( Eunyoung Tak ),( Gi-won Song ),( Ki-hun Kim ),( Chul-soo Ahn ),( Deok-bog Moon ),( Tae-yong Ha ),( Dong-hwan Jung ),( Gil-chun Park ),( Sung-gyu Lee ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1
Aims: We investigated metformin-induced cytotoxic effects in vitro and assessed the chemopreventive effects of metformin in patients undergoing hepatic resection (HR) for hepatocellular carcinoma (HCC). Methods: This study consisted of two independent parts: a laboratory research and a clinical study to assess the antitumor effects of metformin. The laboratory research assessed whether exposure to metformin has any cytotoxic effect on liver tumor cell lines. In the clinical study, the rate of tumor recurrence and overall patient survival after HR of HCC were investigated to assess whether long-term exposure to metformin has any chemopreventive effects. Results: In vitro study using HCC cell lines revealed noticeable cytotoxic effects of metformin, which were largely weaker than those of sorafenib. In the clinical study, no statistical differences were found in tumor recurrence or overall survival between metformin and control groups. In contrast, there was a non-significant difference in tumor recurrence between metformin and propensity score-matched control groups, but there was significant difference in overall patient survival. Metformin administration was an independent risk factor for patient survival. Conclusions: In conclusion, our in vitro laboratory study demonstrated presence of cytotoxic effects of metformin. Metformin administration was associated with reduced tumor recurrence and helped induce significant improvements in overall patient survival in patients who underwent HR for HCC.
Cereblon as a Novel Prognostic Biomarker for Small Hepatocellular Carcinoma
( Shin Hwang ),( Sung-hwa Kang ),( Kyong-jin Lee ),( Eunyoung Tak ),( Young-joo Lee ),( Ki-hun Kim ),( Chul-soo Ahn ),( Deog-bog Moon ),( Tae-yong Ha ),( Gi-won Song ),( Dong-hwan Jung ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1
Aims: Cereblon is a substrate receptor of the E3 ubiquitin ligase complex and functions as a metabolic regulator, directly interacting with AMP-activated protein kinase (AMPK) α1 and inhibiting AMPK activation. We raise a hypothesis that cereblon is a biomarker for hepatocellular carcinoma (HCC). Methods: We developed CRBN-specific monoclonal primary antibody to detect cereblon at the tissue samples (Korea patent). After immunocytochemical staining and Western blot assay, cereblon was quantitatively measured. We performed two development cohort studies to find out the role of cereblon as a diagnostic and prognostic biomarker for HCC. The cutoff of cereblon expression was set to be 2 folds comparing with that at the surrounding liver tissue. Results: One development cohort included 40 patients who underwent macroscopic curative resection for HCC of 7<sup>th</sup> AJCC stage I or II. The profiles of patients in stage I and II groups were similar each other. There was no significant difference in tumor recurrence (P=0.14) and patient survival (P=0.33) between the stage I and II groups. Higher cereblon expression was observed in 19 (47.5%). High cereblon expression group showed higher recurrence (P=0.017) and lower survival (P=0.025) rates than low cereblon expression group. The hazard ratio of cereblon was estimated to 3.5 (P=0.035). Another development cohort study for response treatment to sorafenib was performed, in which cereblon does not appear to be a reliable response biomarker so far. Conclusions: The post-resection prognostic impact of cereblon was greater than that of microvascular invasion in solitary HCCs. We think that cereblon can be an independent biomarker to predict post-resection prognosis even in patients with early or small HCCs. Further high-volume validation study is necessary to investigate the role of cereblon in HCC.
( Shin Hwang Sang ),( Hyun Kang Young ),( Joo Lee Ki ),( Hun Kim Chul ),( Soo Ahn Deok ),( Bog Moon Tae ),( Yong Ha Gi ),( Won Song Dong ),( Hwan Jung Sung ),( Gyu Lee ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1
Aims: Several important changes were made to the 8th edition of American Joint Commission on Cancer (AJCC) tumor staging system for intrahepatic cholangiocarcinoma (ICC). We assessed the prognostic impact of this new tumor staging system compared to the 7th edition. Methods: A retrospective single-institution study was performed with 626 patients who underwent R0 resection for ICC over 20-year period. Results: Anatomical resection and concurrent bile duct resection were performed in 571 (91.2%) and 62 (9.9%) patients, respectively. Cumulative tumor recurrence and patient survival rates were 40.6% and 73.3% at 1 year; 66.7% and 43.8% at 3 years; 73.6% and 30.4% at 5 years; and 74.4% and 20.3% at 10 years, respectively. Independent prognostic factors for tumor recurrence and patient survival were multiple tumors, CA 19-9 >200 U/mL, tumor size >5 cm, direct invasion to extrahepatic structure, and lymph node metastasis. For TNM stages in the 7th versus the 8th editions, C-index was 0.615 and 0.625 for tumor recurrence and 0.626 and 0.628 for patient survival, respectively. Conclusions: The 8th edition AJCC appears to provide high prognostic contrast for T stage categories, except for T3. However, overall prognostic performance of the 8th edition was not markedly improved over the 7th edition.