1.Isolation and characterization of cancer-associated fibroblasts in the tumor microenvironment of hepatocellular carcinoma
Kyoungdo MUN ; Jiwon HAN ; Pureun ROH ; Jonggeun PARK ; Gahee KIM ; Wonhee HUR ; Jeongwon JANG ; Jongyoung CHOI ; Seungkew YOON ; Youngkyoung YOU ; Hojoong CHOI ; Pilsoo SUNG
Journal of Liver Cancer 2023;23(2):341-349
Background:
/Aim: Cancer-associated fibroblasts (CAFs) play an immunosuppressive role in the tumor microenvironment (TME) of human cancers; however, their characteristics and role in hepatocellular carcinoma (HCC) remain to be elucidated.
Methods:
Nine tumor and surrounding liver tissue samples from patients with HCC who underwent surgery were used to isolate patient-derived CAFs. Cell morphology was observed using an optical microscope after culture, and cell phenotypes were evaluated using flow cytometry and immunoblotting. Cytokines secreted by CAFs into culture medium were quantified using a multiplex cytokine assay.
Results:
CAFs were abundant in the TME of HCC and were adjacent to immune cells. After culture, the CAFs and non-tumor fibroblasts exhibited spindle shapes. We observed a robust expression of alpha-smooth muscle actin and fibroblast activation protein in CAFs, whereas alpha-fetoprotein, epithelial cell adhesion molecule, platelet/endothelial cell adhesion molecule-1, and E-cadherin were not expressed in CAFs. Furthermore, CAFs showed high secretion of various cytokines, namely C-X-C motif chemokine ligand 12, interleukin (IL)-6, IL-8, and C-C motif chemokine ligand 2.
Conclusions
CAFs are abundant in the TME of HCC and play a crucial role in tumor progression. These fibroblasts secrete cytokines that promote tumor growth and metastasis.
2.Upregulation of the Vitamin D Receptor in the Nasal Mucosa of Patients With Allergic Rhinitis
Hyeon Geun KIM ; Da Bin LEE ; Tae Hoon LEE ; Bo Yoon CHOI ; Mun Soo HAN ; Sang Hag LEE ; Tae Hoon KIM
Journal of Rhinology 2021;28(3):141-146
Background and Objectives:
Vitamin D modulates immunity, including that of allergic diseases, and plays its roles through contact with vitamin D receptors (VDR). Recent studies have shown that patients with allergic rhinitis have low systemic serum vitamin D level. However, the expression of VDR in local tissue such as human nasal mucosa has not been investigated. Our study demonstrated that, in nasal mucosa of normal controls and patients with allergic rhinitis.
Materials and Methods:
Nasal mucosa were harvested from twenty-five patients who had normal nasal mucosa and twenty-five patients with allergic rhinitis. After the total RNA isolation, we performed reverse transcriptase-polymerase chain reaction, immunohistochemical staining and western blot analysis.
Results:
VDR were expressed in submucosal glands and the superficial layer of epithelial cell, and that inflammatory cells are expressed more highly in the nasal mucosa of patients with allergic rhinitis compared to those without. In the mucosa of patients with allergic rhinitis, VDR expression level was upregulated compared to that in normal nasal mucosa.
Conclusion
This findings suggest that VDR plays a role in the pathogenesis of allergic rhinitis. Additional research is needed to determine the mechanism and consequences of VDR upregulation.
3.Genotoxicity in Patients on Long-term Proton Pump Inhibitor Therapy in Korea: A Nested Case-control, Prospective, Pilot Study
Youn I CHOI ; Jun-Won CHUNG ; Dong Kyun PARK ; Kyoung Oh KIM ; Kwang An KWON ; Yoon Jae KIM ; Su Young KIM ; Sung-Min AHN ; Mun-Deok HAN ; Kwang-Pil KO
The Korean Journal of Helicobacter and Upper Gastrointestinal Research 2020;20(1):47-53
Background/Aims:
Although proton pump inhibitors (PPIs) remain a mainstay for the suppression of gastric acid secretion, long-term PPI use is associated with side effects. However, the genotoxicity associated with long-term PPI use is unclear.
Materials and Methods:
This prospective observational pilot study enrolled patients who had been on PPIs for >1 year and healthy controls from July 2015 to August 2016. The subjects completed self-report questionnaires pertaining to their drug and medical history, and only those with no medical history and a ≥2-year wash-out period (for drugs other than PPIs) were included. We collected peripheral-blood lymphocytes from long-term PPI users and healthy controls and analyzed the genotoxicity by using the cytokinesis-block micronucleus cytome assay; we also determined the fasting serum levels of pyridoxine, folate, cobalamin, and homocysteine.
Results:
Ten long-term PPI users and 40 healthy control subjects were enrolled. The median serum pyridoxine, folate, cobalamin, and homocysteine levels were not significantly different between the groups. The median frequencies of micronuclei (MNi), nucleoplasmic bridges (NPBs), and nuclear buds (Nbuds) per 1,000 binucleated cells, in long-term PPI users and healthy controls, were 30.3 and 16.3 (P<0.005), 2.5 and 1.8 (P<0.005), and 9.3 and 5.0 (P<0.005), respectively. Even after adjustment for confounding factors, the OR of the MNi, NPBs, and Nbuds for long-term PPI users compared with healthy control subjects were 14.1 (P<0.001), 2.0 (P=0.001), and 1.3 (P=0.3), respectively.
Conclusions
Long-term PPI use was significantly associated with an increased risk of genotoxicity after adjustment for age, sex, body mass index, medical history, drug history, and the serum levels of vitamins.
4.Factors Affecting Endoscopic Curative Resection of Gastric Cancer in the Population-Based Screening Era.
Yoon Gwon MUN ; Myung Gyu CHOI ; Chul Hyun LIM ; Han Hee LEE ; Dong Hoon KANG ; Jae Myung PARK ; Kyo Young SONG
Clinical Endoscopy 2018;51(5):478-484
BACKGROUND/AIMS: Since population-based screening for gastric cancer in Korea was implemented, endoscopic treatment of early gastric cancer has become increasingly popular. This study investigates factors affecting endoscopic curative resection of early gastric cancer in population-based screening for gastric cancer. METHODS: We retrospectively reviewed data of patients with newly diagnosed gastric cancer who underwent treatment at Seoul St. Mary’s Hospital. All patients completed questionnaires about clinical information, including interval between surveillance tests for gastric cancer. RESULTS: Of 469 gastric cancer patients, 147 (31.3%) had undergone curative endoscopic resection, 260 (55.4%) had undergone curative surgical resection, and 62 (13.3%) underwent non-curative resection or were in an inoperable state. Patients with curative endoscopic resection had fewer alarm symptoms/signs than other groups. In multivariate analysis, regular surveillance endoscopy was the only factor predicting curative endoscopic resection (odds ratio [OR], 6.099; 95% confidence interval [CI], 2.532–14.933). In addition, patients undergoing gastric cancer screening had a significantly higher rate of endoscopic curative resection compared with subjects who had never been screened. (1-year interval: OR, 49.969; 95% CI, 6.340–393.827, 2-year interval: OR, 15.283; 95% CI, 1.833–127.406, over 2-year interval: OR, 10.651; 95% CI, 1.248–90.871). Shorter screening test intervals were associated with higher rates of endoscopic curative resection. CONCLUSIONS: Regular surveillance testing was the independent factor predicting curative endoscopic resection of gastric cancer.
Early Detection of Cancer
;
Endoscopy
;
Humans
;
Korea
;
Mass Screening*
;
Multivariate Analysis
;
Retrospective Studies
;
Seoul
;
Stomach Neoplasms*
5.Classification of Lacrimal Punctal Stenosis and Its Related Histopathological Feature in Patients with Epiphora.
Mun Chong HUR ; Sang Wook JIN ; Mi Sook ROH ; Woo Jin JEONG ; Won Yeol RYU ; Yoon Hyung KWON ; Hee Bae AHN
Korean Journal of Ophthalmology 2017;31(5):375-382
PURPOSE: To evaluate the classification of punctal stenosis based on the shape of the external punctum, clinical characteristics and histopathologic features. METHODS: Patients who experienced tearing and were diagnosed with punctal stenosis were evaluated in this study. Punctal stenosis was classified according to the shape of the lower external punctum, which included membranous type, slit type, horseshoe type, and pinpoint type. Tear meniscus height, 2% fluorescein dye disappearance test and lacrimal pathway irrigation were measured or performed. For treatment, a punctal snip operation and silicone tube placement were performed, and the peripunctal histopathological findings were evaluated. RESULTS: Punctal stenosis was classified into four types: membranous type (17 eyes, 21.5%), slit type (11 eyes, 13.9%), horseshoe type (25 eyes, 31.6%), and pinpoint type (26 eyes, 32.9%). The tear meniscus was significantly higher, and the 2% fluorescein dye disappeared significantly more slowly in the punctal stenosis group. However, correlation of the tear meniscus height and 2% fluorescein dye disappearance test with the punctum shape was not statistically significant. A history of previous chemotherapy was significantly associated with the occurrence of punctal stenosis, especially the membranous type (p < 0.05). Histopathologic evaluation of the punctum showed differences between the punctum types. Pinpoint puncta exhibited a high density of muscle fibers, while they were faintly visible in the membranous type. CONCLUSIONS: Acquired punctal stenosis has various shapes, and the major types of stenotic puncta exhibited unique histopathologic features. Punctal stenosis and its pathophysiology may be related to multiple factors, such as age and systemic 5-fluorouracil chemotherapy history.
Classification*
;
Constriction, Pathologic*
;
Drug Therapy
;
Fluorescein
;
Fluorouracil
;
Humans
;
Lacrimal Apparatus
;
Lacrimal Apparatus Diseases*
;
Silicon
;
Silicones
;
Tears
6.An unusual case of candidemia presenting as acute respiratory distress syndrome after a small bowel bezoar removal operation.
Yun Su MUN ; Moon Soo LEE ; Joo Seung PARK ; Jun Wan LEE ; Sun Young JUNG ; Hee Jung YOON ; Hyun Young HAN
Annals of Surgical Treatment and Research 2015;88(1):48-51
We report a rare case of sepsis with acute respiratory distress syndrome (ARDS) caused by Candida parapsilosis and Candida famata after a small bowel bezoar operation. The patient was successfully treated with intensive care including mechanical ventilation and systemic antifungal therapy. A strong association was observed between the intestinal obstruction caused by the bezoar and candidemia presenting as ARDS. This is the first case in which candidemia has led to ARDS after a bezoar removal operation in a patient who was neither immunocompromised nor self-administering an illicit intravenous drug.
Bezoars*
;
Candida
;
Candidemia*
;
Humans
;
Critical Care
;
Intestinal Obstruction
;
Respiration, Artificial
;
Respiratory Distress Syndrome, Adult*
;
Sepsis
7.Comparison of Multi-Echo Dixon Methods with Volume Interpolated Breath-Hold Gradient Echo Magnetic Resonance Imaging in Fat-Signal Fraction Quantification of Paravertebral Muscle.
Yeon Hwa YOO ; Hak Sun KIM ; Young Han LEE ; Choon Sik YOON ; Mun Young PAEK ; Hanna YOO ; Stephan KANNENGIESSER ; Tae Sub CHUNG ; Ho Taek SONG ; Jin Suck SUH ; Sungjun KIM
Korean Journal of Radiology 2015;16(5):1086-1095
OBJECTIVE: To assess whether multi-echo Dixon magnetic resonance (MR) imaging with simultaneous T2* estimation and correction yields more accurate fat-signal fraction (FF) measurement of the lumbar paravertebral muscles, in comparison with non-T2*-corrected two-echo Dixon or T2*-corrected three-echo Dixon, using the FF measurements from single-voxel MR spectroscopy as the reference standard. MATERIALS AND METHODS: Sixty patients with low back pain underwent MR imaging with a 1.5T scanner. FF mapping images automatically obtained using T2*-corrected Dixon technique with two (non-T2*-corrected), three, and six echoes, were compared with images from single-voxel MR spectroscopy at the paravertebral muscles on levels L4 through L5. FFs were measured directly by two radiologists, who independently drew the region of interest on the mapping images from the three sequences. RESULTS: A total of 117 spectroscopic measurements were performed either bilaterally (57 of 60 subjects) or unilaterally (3 of 60 subjects). The mean spectroscopic FF was 14.3 +/- 11.7% (range, 1.9-63.7%). Interobserver agreement was excellent between the two radiologists. Lin's concordance correlation between the spectroscopic findings and all the imaging-based FFs were statistically significant (p < 0.001). FFs obtained from the T2*-corrected six-echo Dixon sequences showed a significantly better concordance with the spectroscopic data, with its concordance correlation coefficient being 0.99 and 0.98 (p < 0.001), as compared with two- or three-echo methods. CONCLUSION: T2*-corrected six-echo Dixon sequence would be a better option than two- or three-echo methods for noninvasive quantification of lumbar muscle fat quantification.
Adult
;
Aged
;
Aged, 80 and over
;
Female
;
Humans
;
Image Processing, Computer-Assisted
;
Low Back Pain/*radiography
;
Magnetic Resonance Imaging/instrumentation/*methods
;
Male
;
Middle Aged
;
Muscles/radiography
;
Spinal Cord
8.Breast Metastases from Extramammary Malignancies: Typical and Atypical Ultrasound Features.
Sung Hee MUN ; Eun Young KO ; Boo Kyung HAN ; Jung Hee SHIN ; Suk Jung KIM ; Eun Yoon CHO
Korean Journal of Radiology 2014;15(1):20-28
Breast metastases from extramammary malignancies are uncommon. The most common sources are lymphomas/leukemias and melanomas. Some of the less common sources include carcinomas of the lung, ovary, and stomach, and infrequently, carcinoid tumors, hypernephromas, carcinomas of the liver, tonsil, pleura, pancreas, cervix, perineum, endometrium and bladder. Breast metastases from extramammary malignancies have both hematogenous and lymphatic routes. According to their routes, there are common radiological features of metastatic diseases of the breast, but the features are not specific for metastases. Typical ultrasound (US) features of hematogenous metastases include single or multiple, round to oval shaped, well-circumscribed hypoechoic masses without spiculations, calcifications, or architectural distortion; these masses are commonly located superficially in subcutaneous tissue or immediately adjacent to the breast parenchyma that is relatively rich in blood supply. Typical US features of lymphatic breast metastases include diffusely and heterogeneously increased echogenicities in subcutaneous fat and glandular tissue and a thick trabecular pattern with secondary skin thickening, lymphedema, and lymph node enlargement. However, lesions show variable US features in some cases, and differentiation of these lesions from primary breast cancer or from benign lesions is difficult. In this review, we demonstrate various US appearances of breast metastases from extramammary malignancies as typical and atypical features, based on the results of US and other imaging studies performed at our institution. Awareness of the typical and atypical imaging features of these lesions may be helpful to diagnose metastatic lesions of the breast.
Adenocarcinoma/secondary/ultrasonography
;
Adolescent
;
Adult
;
Breast Neoplasms/*secondary/*ultrasonography
;
Breast Neoplasms, Male/secondary/ultrasonography
;
Carcinoma/secondary/ultrasonography
;
Female
;
Humans
;
Lymphatic Metastasis/ultrasonography
;
Lymphoma, Extranodal NK-T-Cell/pathology/ultrasonography
;
Lymphoma, Large B-Cell, Diffuse/pathology/ultrasonography
;
Male
;
Melanoma/secondary
;
Middle Aged
;
Multiple Myeloma/secondary/ultrasonography
;
Neoplastic Cells, Circulating/pathology
9.Differentiation between Focal Malignant Marrow-Replacing Lesions and Benign Red Marrow Deposition of the Spine with T2*-Corrected Fat-Signal Fraction Map Using a Three-Echo Volume Interpolated Breath-Hold Gradient Echo Dixon Sequence.
Yong Pyo KIM ; Stephan KANNENGIESSER ; Mun Young PAEK ; Sungjun KIM ; Tae Sub CHUNG ; Yeon Hwa YOO ; Choon Sik YOON ; Ho Taek SONG ; Young Han LEE ; Jin Suck SUH
Korean Journal of Radiology 2014;15(6):781-791
OBJECTIVE: To assess the feasibility of T2*-corrected fat-signal fraction (FF) map by using the three-echo volume interpolated breath-hold gradient echo (VIBE) Dixon sequence to differentiate between malignant marrow-replacing lesions and benign red marrow deposition of vertebrae. MATERIALS AND METHODS: We assessed 32 lesions from 32 patients who underwent magnetic resonance imaging after being referred for assessment of a known or possible vertebral marrow abnormality. The lesions were divided into 21 malignant marrow-replacing lesions and 11 benign red marrow depositions. Three sequences for the parameter measurements were obtained by using a 1.5-T MR imaging scanner as follows: three-echo VIBE Dixon sequence for FF; conventional T1-weighted imaging for the lesion-disc ratio (LDR); pre- and post-gadolinium enhanced fat-suppressed T1-weighted images for the contrast-enhancement ratio (CER). A region of interest was drawn for each lesion for parameter measurements. The areas under the curve (AUC) of the parameters and their sensitivities and specificities at the most ideal cutoff values from receiver operating characteristic curve analysis were obtained. AUC, sensitivity, and specificity were respectively compared between FF and CER. RESULTS: The AUCs of FF, LDR, and CER were 0.96, 0.80, and 0.72, respectively. In the comparison of diagnostic performance between the FF and CER, the FF showed a significantly larger AUC as compared to the CER (p = 0.030), although the difference of sensitivity (p = 0.157) and specificity (p = 0.157) were not significant. CONCLUSION: Fat-signal fraction measurement using T2*-corrected three-echo VIBE Dixon sequence is feasible and has a more accurate diagnostic performance, than the CER, in distinguishing benign red marrow deposition from malignant bone marrow-replacing lesions.
Adult
;
Aged
;
Aged, 80 and over
;
Area Under Curve
;
Bone Marrow Cells/cytology
;
Bone Marrow Transplantation
;
Contrast Media/diagnostic use
;
Diagnosis, Differential
;
Female
;
Humans
;
*Magnetic Resonance Imaging
;
Male
;
Middle Aged
;
ROC Curve
;
Sensitivity and Specificity
;
Signal-To-Noise Ratio
;
Spinal Diseases/diagnosis/*radiography
10.A Case of Hereditary Spherocytosis Coexisting with Gilbert's Syndrome.
Min Jae LEE ; Yoon Hwan CHANG ; Seung Hwa KANG ; Se Kwon MUN ; Heyjin KIM ; Chul Ju HAN ; Jin KIM ; Hye Jin KANG
The Korean Journal of Gastroenterology 2013;61(3):166-169
We recently encountered a case of hereditary spherocytosis coexisting with Gilbert's syndrome. Patient was initially diagnosed with Gilbert's syndrome and observed, but other findings suggestive of concurrent hemolysis, such as splenomegaly and gallstones were noted during the follow-up period. Therefore, further evaluations, including a peripheral blood smear, osmotic fragility test, autohemolysis test, and red blood cell membrane protein test were performed, and coexisting hereditary spherocytosis was diagnosed. Genotyping of the conjugation enzyme uridine diphosphate-glucuronosyltransferase was used to confirm Gilbert's syndrome. Because of the high prevalence rates and similar symptoms of these 2 diseases, hereditary spherocytosis can be masked in patients with Gilbert's syndrome. In review of a case and other article, the possibility of the coexistence of these 2 diseases should be considered, especially in patients with unconjugated hyperbilirubinemia who also have splenomegaly and gallstones.
Adult
;
Erythrocytes/physiology
;
Gallstones/etiology
;
Genotype
;
Gilbert Disease/complications/*diagnosis/genetics
;
Glucuronosyltransferase/genetics
;
Hemolysis
;
Humans
;
Hyperbilirubinemia/etiology
;
Male
;
Polymorphism, Single Nucleotide
;
Spherocytosis, Hereditary/complications/*diagnosis/genetics
;
Splenomegaly/etiology

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