1.Docosahexaenoic Acid Inhibits Cytokine Expression by Reducing Reactive Oxygen Species in Pancreatic Stellate Cells
Sun Ah CHUNG ; Joo Weon LIM ; Hyeyong KIM
Journal of Cancer Prevention 2021;26(3):195-206
Pancreatic stellate cells (PSCs) are activated by inflammatory stimuli, such as TNF-α or viral infection. Activated PSCs play a crucial role in the development of chronic pancreatitis. Polyinosinic-polycytidylic acid (poly (I:C)) is structurally similar to double-stranded RNA and mimics viral infection. Docosahexaenoic acid (DHA) exhibits anti-inflammatory activity. It inhibited fibrotic mediators and reduced NF-κB activity in the pancreas of mice with chronic pancreatitis. The present study aimed to investigate whether DHA could suppress cytokine expression in PSCs isolated from rats. Cells were pre-treated with DHA or the antioxidant N-acetylcysteine (NAC) and stimulated with TNF-α or poly (I:C). Treatment with TNF-α or poly (I:C) increased the expression of monocyte chemoattractant protein 1 (MCP-1) and chemokine C-X3-C motif ligand 1 (CX3CL1), which are known chemoattractants, and enhanced intracellular and mitochondrial reactive oxygen species (ROS) production and NF-κB activity, but reduced mitochondrial membrane potential (MMP). Increased intracellular and mitochondrial ROS accumulation, cytokine expression, MMP disruption, and NF-κB activation were all prevented by DHA in TNF-α- or poly (I:C)-treated PSCs. NAC suppressed TNF-α- or poly (I:C)-induced expression of MCP-1 and CX3CL1. In conclusion, DHA inhibits poly (I:C)- or TNF-α-induced cytokine expression and NF-κB activation by reducing intracellular and mitochondrial ROS in PSCs. Consumption of DHA-rich foods may be beneficial in preventing chronic pancreatitis by inhibiting cytokine expression in PSCs.
2.Docosahexaenoic Acid Inhibits Cytokine Expression by Reducing Reactive Oxygen Species in Pancreatic Stellate Cells
Sun Ah CHUNG ; Joo Weon LIM ; Hyeyong KIM
Journal of Cancer Prevention 2021;26(3):195-206
Pancreatic stellate cells (PSCs) are activated by inflammatory stimuli, such as TNF-α or viral infection. Activated PSCs play a crucial role in the development of chronic pancreatitis. Polyinosinic-polycytidylic acid (poly (I:C)) is structurally similar to double-stranded RNA and mimics viral infection. Docosahexaenoic acid (DHA) exhibits anti-inflammatory activity. It inhibited fibrotic mediators and reduced NF-κB activity in the pancreas of mice with chronic pancreatitis. The present study aimed to investigate whether DHA could suppress cytokine expression in PSCs isolated from rats. Cells were pre-treated with DHA or the antioxidant N-acetylcysteine (NAC) and stimulated with TNF-α or poly (I:C). Treatment with TNF-α or poly (I:C) increased the expression of monocyte chemoattractant protein 1 (MCP-1) and chemokine C-X3-C motif ligand 1 (CX3CL1), which are known chemoattractants, and enhanced intracellular and mitochondrial reactive oxygen species (ROS) production and NF-κB activity, but reduced mitochondrial membrane potential (MMP). Increased intracellular and mitochondrial ROS accumulation, cytokine expression, MMP disruption, and NF-κB activation were all prevented by DHA in TNF-α- or poly (I:C)-treated PSCs. NAC suppressed TNF-α- or poly (I:C)-induced expression of MCP-1 and CX3CL1. In conclusion, DHA inhibits poly (I:C)- or TNF-α-induced cytokine expression and NF-κB activation by reducing intracellular and mitochondrial ROS in PSCs. Consumption of DHA-rich foods may be beneficial in preventing chronic pancreatitis by inhibiting cytokine expression in PSCs.
3.Investigation into the Possible Genetic Role of Serotonin and Dopamine Transporters in Psychological Resilience.
Sang Hyun CHO ; Jae Kyung CHUNG ; Yang Weon BANG ; Eun Jeong JOO
Journal of the Korean Society of Biological Psychiatry 2018;25(1):16-20
OBJECTIVES: Psychological resilience is the ability to cope with stress. The genetic background behind psychological resilience is not much known. The serotonin transporter and dopamine transporter are implicated in stress related psychology and emotional processing. The aim of this study is to investigate a possible genetic role of functional polymorphisms of serotonin and dopamine transporters for psychological resilience. METHODS: A total of 951 healthy adult subjects were included. Psychological resilience was measured using Connor-Davidson Resilience Scale (CD-RISC). Genotyping was performed for serotonin transporter gene (SERT) promoter variable number tandem repeat (VNTR) and dopamine transporter gene (DAT1) 3'-untranslated region (UTR) VNTR. Genetic association analysis was conducted between genotypes and the CD-RISC score. RESULTS: No genetic association was observed for SERT promoter VNTR or DAT1 3'-UTR VNTR with CD-RISC score. No genetic interaction between SERT promoter VNTR and DAT1 3'-UTR VNTR with CD-RISC score was detected. CONCLUSIONS: Either serotonin or dopamine transporter did not seem to play a significant role for psychological resilience in this sample.
Adult
;
Dopamine Plasma Membrane Transport Proteins
;
Dopamine*
;
Genetic Background
;
Genotype
;
Humans
;
Psychology
;
Resilience, Psychological*
;
Serotonin Plasma Membrane Transport Proteins
;
Serotonin*
;
Tandem Repeat Sequences
4.Identification of Patients with Recurrent Epithelial Ovarian Cancer Who Will Benefit from More Than Three Lines of Chemotherapy
Aeran SEOL ; Ga Won YIM ; Joo Yeon CHUNG ; Se Ik KIM ; Maria LEE ; Hee Seung KIM ; Hyun Hoon CHUNG ; Jae-Weon KIM ; Noh Hyun PARK ; Yong Sang SONG
Cancer Research and Treatment 2022;54(4):1219-1229
Purpose:
This study aimed to identify patients who would benefit from third and subsequent lines of chemotherapy in recurrent epithelial ovarian cancer (EOC).
Materials and Methods:
Recurrent EOC patients who received third, fourth, or fifth-line palliative chemotherapy were retrospectively analyzed. Patients’ survival outcomes were assessed according to chemotherapy lines. Based on the best objective response, patients were divided into good-response (stable disease or better) and poor response (progressive disease or those who died before response assessment) groups. Survival outcomes were compared between the two groups, and factors associated with chemotherapy responses were investigated.
Results:
A total of 189 patients were evaluated. Ninety-four and 95 patients were identified as good and poor response group respectively, during the study period of 2008 to 2021. The poor response group showed significantly worse progression-free survival (median, 2.1 months vs. 9.7 months; p < 0.001) and overall survival (median, 5.0 months vs. 22.9 months; p < 0.001) compared with the good response group. In multivariate analysis adjusting for clinicopathologic factors, short treatment-free interval (TFI) (hazard ratio [HR], 5.557; 95% confidence interval [CI], 2.403 to 12.850), platinum-resistant EOC (HR, 2.367; 95% CI, 1.017 to 5.510), and non-serous/endometrioid histologic type (HR, 5.045; 95% CI, 1.152 to 22.088) were identified as independent risk factors for poor response. There was no difference in serious adverse events between good and poor response groups (p=0.167).
Conclusion
Third and subsequent lines of chemotherapy could be carefully considered for palliative purposes in recurrent EOC patients with serous or endometrioid histology, initial platinum sensitivity, and long TFIs from the previous chemotherapy regimen.
5.Midkine Gene Expression in Gastric Cancer Tissues.
Hyun Joo KWAK ; Yong Bae KIM ; Byung Soh MIN ; Ho Young MAENG ; Sung Hoon SONG ; Hye Weon CHUNG ; Tae Soo KIM ; Hei Cheol CHUNG ; Sun Young RHA ; Hyun Cheol CHUNG ; Sung Hoon NOH ; Joo Hang KIM ; Jae Kyung ROH ; Jin Sik MIN ; Byung Soo KIM
Journal of the Korean Cancer Association 1997;29(2):204-211
PURPOSE: We evaluated the clinical significance of the tumor growth factor, midkine (MK), in paired gastric cancer and normal tissues. MATERIALS AND METHODS: Twenty paired normal and cancer tissues were tested for MK mRNA expression by Northern blot analysis. Vessel staining was done by immunohistochemical staining using CD-31 monoclonal antibody (Dako). RESULTS: MK mRNA was mainly expressed in cancer tissues (11 versus 1). Lymph node metastasis, pathological stage and tumor differentiation did not correlate with MK expression. However, MK expression rate increased with increment in tumor size (p=0.05). Microvascular density did not correlate with tumor invasion, lymph node metastasis, and pathological stages. However, there was a tendency of vascular density increment with MK expression in T1-T2 stage. CONCLUSION: MK was mainly expressed in larger gastric cancer tissues suggesting its role in cancer growth in vivo. But no definite correlation between MK expression and tumor microvascular density was found.
Blotting, Northern
;
Gene Expression*
;
Lymph Nodes
;
Neoplasm Metastasis
;
RNA, Messenger
;
Stomach Neoplasms*
6.Current Trends in the Incidence and Survival Rate of Urological Cancers in Korea.
Jae Young JOUNG ; Jiwon LIM ; Chang Mo OH ; Kyu Won JUNG ; Hyunsoon CHO ; Sung Han KIM ; Ho Kyung SEO ; Weon Seo PARK ; Jinsoo CHUNG ; Kang Hyun LEE ; Young Joo WON
Cancer Research and Treatment 2017;49(3):607-615
PURPOSE: This descriptive study assessed the current trends in the incidence of urological cancers and patient survival in Korea. MATERIALS AND METHODS: In this nationwide retrospective observational study based on the data from the Korea National Cancer Incidence Database (KNCIDB), this study analyzed the age-standardized incidence rates (ASRs) and annual percentage changes (APCs) of kidney, bladder, prostate, testicular, and penile cancers as well as cancer of the renal pelvis and ureter between 1999 and 2012. The relative survival rates (RSRs) were calculated for urological cancer patients diagnosed between 1993 and 2012 from the KNCIDB data. RESULTS: Prostate cancer was diagnosed in 66,812 individuals followed by bladder (41,549) and kidney (36,836) cancers. The overall ASR (18.26 per 100,000) increased with age because of the higher ASRs of bladder and prostate cancers in the elderly. The ASR for kidney cancer was highest in the 40-59-year-old group, whereas testicular cancer occurred most frequently before the age of 40. The incidence of most urological cancers increased (overall APC, 6.39%; p < 0.001), except for penile (APC, –2.01%; p=0.05) and bladder (APC, –0.40%; p=0.25) cancers. The overall survival increased steadily (5-year RSR, 66.4% in 1993-1995 vs. 84.2% in 2008-2012; p < 0.001), particularly for prostate (by 34.10%) and kidney (by 16.30%) cancers, but not for renal pelvis and ureter cancers (–7.20%). CONCLUSION: The most common urological cancer in Korea was prostate cancer followed by bladder and kidney cancers. The incidence of most urological cancers, except for penile and bladder cancers, increased. Survival also increased, particularly for prostate and kidney cancers.
Aged
;
Humans
;
Incidence*
;
Kidney
;
Kidney Neoplasms
;
Kidney Pelvis
;
Korea*
;
Male
;
Observational Study
;
Penile Neoplasms
;
Prostate
;
Prostatic Neoplasms
;
Retrospective Studies
;
Survival Rate*
;
Testicular Neoplasms
;
Ureter
;
Ureteral Neoplasms
;
Urinary Bladder
;
Urinary Bladder Neoplasms
;
Urologic Neoplasms*
7.A Promising Method for Tumor Localization during Total Laparoscopic Distal Gastrectomy: Preoperative Endoscopic Clipping based on Negative Biopsy and Selective Intraoperative Radiography Findings.
Joo Weon CHUNG ; Kyung Won SEO ; Kyoungwon JUNG ; Moo In PARK ; Sung Eun KIM ; Seun Ja PARK ; Sang Ho LEE ; Yeon Myung SHIN
Journal of Gastric Cancer 2017;17(3):220-227
PURPOSE: Precise localization of tumors and creation of sufficient proximal resection margins are complicated processes during total laparoscopic distal gastrectomy (TLDG) for clinical T1/T2 gastric cancers. Various solutions to this problem have also yielded many disadvantages. In this study, we reviewed a preoperative endoscopic clipping method based on the results of negative biopsy and selective intraoperative radiography. MATERIALS AND METHODS: A retrospective review of 345 consecutive patients who underwent TLDG and preoperative endoscopic clipping for tumor localization was conducted. During preoperative endoscopy, the endoscopists performed negative biopsies just 1–2 cm selectively above the tumor's upper limit. After confirming the biopsy results, endoscopic metal clips were applied just proximal to the negative biopsy site the day before surgery. Selective intraoperative tumor localization using portable abdominal radiography was performed only when we could not ensure a precise resection line. RESULTS: Negative biopsy was performed in 244 patients. Larger tumor size (P=0.008) and more distally located tumors (P=0.052) were observed more frequently in the negative biopsy group than in the non-negative biopsy group. The non-negative biopsy group had significantly higher frequencies of differentiated tumor types than the negative biopsy group (P=0.003). Of the 244 patients who underwent negative biopsies, 6 had cancer cells in their biopsy specimens. We performed intraoperative radiography in 12 patients whose tumors had difficult-to-determine proximal margins. No tumors were found in the proximal resection margins of any patients. CONCLUSIONS: Our tumor localization method is a promising and accurate method for securing a sufficient resection margin during TLDG.
Biopsy*
;
Endoscopy
;
Gastrectomy*
;
Humans
;
Laparoscopy
;
Methods*
;
Radiography*
;
Radiography, Abdominal
;
Retrospective Studies
;
Stomach Neoplasms
8.A Case of Small Cell Carcinoma of Gallbladder.
Woo Bong CHOI ; Tae Young LEE ; Nak Weon LEE ; Il Kwun CHUNG ; Hong Soo KIM ; Sang Hum PARK ; Mun Ho LEE ; Sun Joo KIM ; Dae Jung KIM
Korean Journal of Medicine 1997;53(6):847-852
Carcinoma of the gallbladder is relatively rare malignancy usually found in an elderly, predominantly female population. Histologically, adenocarcinoma predominate, with only 10% to 15% being of other varieties(small cell carcinoma and others). Small cell carcinoma of the gallbladder is a rare lesion and predominantly a disease of older women with clinical history of stones. These tumors show an aggressive clinical course and death usually occurs with in a few months of the diagnosis. The diagnosis of small cell carcinoma should be based on cell morphology, histologic pattern and immunohistochemical study. Correct diagnosis is important not only because these tumors give rise to endocrine syndromes, but also because the chemotherapeutic approach to small cell carcinoma differs from that for adenocarcinoma.
Adenocarcinoma
;
Aged
;
Carcinoma, Small Cell*
;
Diagnosis
;
Female
;
Gallbladder*
;
Humans
9.The Correlation of Tissue-Based Biomarkers in Primary and Metastatic Renal Cell Carcinoma Lesions: A Tissue Microarray Study.
Sung Han KIM ; Weon Seo PARK ; Eun Young PARK ; Boram PARK ; Jungnam JOO ; Jae Young JOUNG ; Ho Kyung SEO ; Kang Hyun LEE ; Jinsoo CHUNG
Korean Journal of Urological Oncology 2016;14(3):152-158
PURPOSE: The study was aimed to determine the correlations of tissue-based biomarker expressions between primary and metastatic specimens of renal cell carcinoma and with several well-known prognostic clinicopathological parameters. MATERIALS AND METHODS: The immunohistochemistry (IHC) was used to determine the expression levels of 9 tissue-based markers calculated in H-score expressed by percentage of expression multiplied by the intensity score (0, 1, 2, and 3 points). Using 17 patients' 38 specimens paired with primary renal lesion and its metastatic lesions collected between 2004 and 2015, Tissue microarray with IHC was performed with BAP1, PBRM1, pS6, PTEN, TGase2, PD-L1, CA9, PSMA, and Ki-67 on formalin-fixed paraffin-embedded sections. Pearson correlation and accuracy test were performed to analyze the correlation between primary and metastatic tissues. RESULTS: The 17 patients' mean age was 56.9 years old, mean tumor size was 7.9 cm, and the male to female ratio was 13:4 (76.5%:23.5%), respectively. Three patients had 2, 3, and 3 metastatic tissues, and the rest of 14 patients had only one metastatic tissue. The H-score (PSMA and Ki67) and intensity score (pS6 and PSMA) showed that some differential significant markers were identified which had statistical correlations of expression levels between primary and metastatic lesions among 9 markers. However, no real correlation of PSMA, Ki67, and pS6 markers were found their expressions of between primary and metastatic tissues because of their skewed expressions. CONCLUSIONS: Tissue markers failed to correlate their expression levels in primary lesions with those of metastatic lesions.
Biomarkers*
;
Carcinoma, Renal Cell*
;
Female
;
Humans
;
Immunohistochemistry
;
Male
;
Neoplasm Metastasis
10.Borrmann Type IV Adenocarcinoma versus Gastric Lymphoma: Spiral CT Evaluation.
Bo Kyoung SEO ; Yun Hwan KIM ; Kue Hee SHIN ; Suk Joo HONG ; Hong Weon KIM ; Cheol Min PARK ; Kyoo Byung CHUNG ; Hyun Deuk CHO
Journal of the Korean Radiological Society 1999;41(6):1155-1160
PURPOSE: To distinguish the spiral CT findings of Borrmann type IV adenocarcinoma from those of gastric lymphoma with diffuse gastric wall thickening. MATERIALS AND METHODS: We retrospectively reviewed the spiral CT scans of 30 patients with Borrmann type IV adenocarcinoma and nine with gastric lymphoma with diffuse gastric wall thickening. In all patients the respective condition was pathologically confirmed by gastrectomy. CT scanning was performed after peroral administration of 500-700ml of water. A total of 120-140ml bolus of nonionic contrast material was administered intravenously at a flow rate of 3ml/sec and two-phase images were obtained at 35-45 sec(early phase) and 180 sec(delayed phase) after the start of bolus injection. Spiral CT was performed with 10mm collimation, 10mm/sec table feed and 10mm reconstruction. We evaluated the degree and homogeneity of enhancement of thickened entire gastric wall, and the enhancement pattern of gastric inner layer, as seen on earlyphase CT scans. On early and delayed views, the thickness of gastric wall and the presence of perigastric fat infiltration were determined. The enhancement patterns of gastric inner layer were classified as either continuous or discontinuous thick enhancement, thin enhancement, or nonenhancement. RESULTS: The thickness of gastric wall was 1.2-3.5cm(mean 2.2cm) in cases of adenocarcinoma and 1.2-7.6c m (mean 4cm) in lymphoma. Perigastric fat infiltration was seen in 24 patients with adenocarcinoma(80 %) and four with lymphoma(44%). In those with adenocarcinoma, the degree of enhancement of entire gastric wall was hyperdense in fifteen patients(50%) and isointense in eleven (37 %). Seven patients with lymphoma(78 % ) showed hypodensity. In those with adenocarcinoma, continuous thick enhancement of gastric inner layer was seen in 18 patients(60 %) and discontinuous thick enhancement in nine(30%). In lymphoma cases, no thick enhancement was observed. Thin enhancement of gastric inner layer was demonstrated in three patients with adenocarcinoma( 10 %) and two with lymphoma(22 %). In seven patients with lymphoma(78 %), there was no enhancement. CONCLUSION: The following early-phase findings are highly suggestive of gastric lymphoma: a gastric wall thickness of more than 3 cm; no or minimal perigastric fat infiltration, hypodense enhancement of thickened entire gastric wall; and no or thin enhancement of gastric inner layer.
Adenocarcinoma*
;
Gastrectomy
;
Humans
;
Lymphoma*
;
Retrospective Studies
;
Tomography, Spiral Computed*
;
Tomography, X-Ray Computed
;
Water