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1.  Mixed Epithelial and Stromal Tumor of the Kidney : A Case Report 
Journal of Korean Medical Science  2007;22(1):159-162.
The descriptive term "mixed epithelial and stromal tumor of the kidney" was recently proposed for a group of renal tumors characterized histologically by a mixture of stromal and epithelial proliferation. It is a rare benign neoplasm of the kidney which has been reported under various names such as adult type mesoblastic nephroma or others. We report a case of mixed epithelial and stromal tumor in a 47 yr old female patient presenting as a partly cystic and partly solid renal mass. Microscopically, the tumor exhibited spindle cell component in solid portion and epithelial proliferation around microcystic areas. Immunoreactive profiles and ultrastructural examination suggested myofibroblastic nature of the stromal cells. We believe this case exemplifies a unique adult renal tumor displaying both epithelial and stromal neoplastic component and has a few unusual features worthy of attention.
doi:10.3346/jkms.2007.22.1.159
PMCID: PMC2693557  PMID: 17297273
Kidney; Nephroma, Mesoblastic; Adult
2.  Expression of Peroxisome Proliferator Activated Receptor gamma in Prostatic Adenocarcinoma 
Journal of Korean Medical Science  2015;30(5):533-541.
Peroxisome proliferator-activated receptor gamma (PPAR-γ), a ligand-activated transcription factor has been investigated as the target for cancer treatment as well as metabolic disorders. Recent studies have demonstrated that PPAR-γ ligands are anti-tumorigenic in prostate cancer due to anti-proliferative and pro-differentiation effects. The aim of this study was to validate PPAR-γ expression in malignant and benign prostate tissues by immunohistochemistry and quantitative real-time polymerase chain reaction (PCR). A total of 730 prostatic adenocarcinomas (PCAs) including 63 whole sections from radical prostatectomy specimens and tissue microarrays containing 667 PCAs were subject to immunostaining for two PPAR-γ antibodies. Twenty-five benign prostate tissues and PCAs were selected for investigating mRNA expression by quantitative real-time PCR. 10.7% of PCAs (78/730) showed cytoplasmic immunoreactivity of PPAR-γ and no nuclear immunoreactivity was noted in PCAs. Most benign prostatic glands showed negative immunoreactivity of PPAR-γ except for variable weak cytoplasmic staining in some glands. Nuclear immunoreactivity of PPAR-γ was noted some central zone and verumontanum mucosal epithelium. The constitutive PPAR-γ mRNA showed significantly lower level in PCAs compared to that in the benign tissues. There was no difference of PPAR-γ mRNA expression between low (≤7) and high (>7) Gleason score groups. There was no association of PPAR-γ mRNA level or cytoplasmic immunostaining with Gleason grade or pathologic stage. Our study supported the evidence of extra-nuclear localization and nongenomic actions of PPAR-γ. Further studies are needed to assess the functional role of PPAR-γ and to validate its therapeutic implication in prostate cancer.
Graphical Abstract
doi:10.3346/jkms.2015.30.5.533
PMCID: PMC4414635  PMID: 25931782
Prostatic Neoplasms; PPAR gamma; Immunohistochemistry; Real-Time Polymerase Chain Reaction
3.  Megalocytic Interstitial Nephritis Following Acute Pyelonephritis with Escherichia coli Bacteremia: A Case Report 
Journal of Korean Medical Science  2014;30(1):110-114.
Megalocytic interstitial nephritis is a rare form of kidney disease caused by chronic inflammation. We report a case of megalocytic interstitial nephritis occurring in a 45-yrold woman who presented with oliguric acute kidney injury and acute pyelonephritis accompanied by Escherichia coli bacteremia. Her renal function was not recovered despite adequate duration of susceptible antibiotic treatment, accompanied by negative conversion of bacteremia and bacteriuria. Kidney biopsy revealed an infiltration of numerous histiocytes without Michaelis-Gutmann bodies. The patient's renal function was markedly improved after short-term treatment with high-dose steroid.
Graphical Abstract
doi:10.3346/jkms.2015.30.1.110
PMCID: PMC4278017  PMID: 25552891
Acute Kidney Injury; Megalocytic Interstitial Nephritis; Interstitial Nephritis
4.  CCAR1 promotes chromatin loading of androgen receptor (AR) transcription complex by stabilizing the association between AR and GATA2 
Nucleic Acids Research  2013;41(18):8526-8536.
Androgen receptor (AR), a ligand-dependent transcription factor, plays a critical role in prostate cancer onset and progression, and its transcriptional function is mediated largely by distinct nuclear receptor co-regulators. Here, we show that cell cycle and apoptosis regulator 1 (CCAR1) functions as an AR co-activator. CCAR1 interacted with and enhanced the transcriptional activity of AR. Depletion of CCAR1 caused reduction in androgen-dependent expression of a subset of AR target genes. We further showed that CCAR1 is required for recruitment of AR, MED1 and RNA polymerase II to the enhancers of AR target genes and for androgen-induced long-range prostate specific antigen enhancer–promoter interaction. The molecular mechanism underlying CCAR1 function in AR-mediated transcription involves CCAR1-mediated enhanced recruitment of GATA2, a pioneer factor for AR, to AR-binding sites. CCAR1 stabilized the interaction between AR and GATA2 by interacting directly with both proteins, thereby facilitating AR and GATA2 occupancy on the enhancers. Furthermore, CCAR1 depletion inhibited the growth, migration, invasion of prostate cancer cells and reduced the tumorigenicity of prostate cancer cells in vivo. Our results firmly established CCAR1 as an AR co-activator that plays a key role in AR transcription complex assembly and has an important physiological role in androgen signaling and prostate tumorigenesis.
doi:10.1093/nar/gkt644
PMCID: PMC3794601  PMID: 23887938
5.  Urothelial eddies in papillary urothelial neoplasms: a distinct morphologic pattern with low risk for progression 
We encountered an undescribed histologic feature of papillary urothelial neoplasms: “urothelial eddy”, which was histologically reminiscent of squamous eddy of irritated follicular keratosis of the skin. A review of 756 patients with transurethral resection of bladder tumor revealed 10 patients (1.3%) of papillary urothelial neoplasms with urothelial eddies. All cases were male with a median age of 65 years. Urothelial eddies were characterized by small ovoid nests of ovoid to spindle cells arranged in an onion-skin pattern with fine cytoplasmic processes within wide intercellular space. The cytoplasmic processes mimicked intercellular bridges but ultrastructurally were cytoplasmic microvillous projections. They were of papillary urothelial neoplasm of low malignant potential in seven patients and low-grade urothelial carcinoma in three patients. Nine patients presented as non-invasive tumor and one patient showed microinvasion within papillary stalks. Six patients showed an inverted growth pattern. Their immunoprofile was more similar to that of conventional urothelial carcinoma rather than squamous cell carcinoma: high expressions of GATA3, S100P, uroplakin III, and cytokeratin 7; and low expressions of high molecular weight cytokeratin and p53. The Ki-67 labeling index was low (mean and median values, 2% each). During the follow-up period (mean, 88.7 months), four patients, including the microinvasive patient, showed recurrence with the same grade and stage but neither progressed into muscle-invasive tumor nor caused death. Our results suggest that urothelial eddy is a rare aberrant histology of papillary urothelial neoplasms with indolent behavior and should be discriminated from squamous differentiation of urothelial carcinoma, which has a poor prognosis.
PMCID: PMC3726961  PMID: 23923064
Urothelial carcinoma; variant; urothelial eddy; indolent
6.  A Novel UMOD Mutation (c.187T>C) in a Korean Family with Juvenile Hyperuricemic Nephropathy 
Annals of Laboratory Medicine  2013;33(4):293-296.
Familial juvenile hyperuricemic nephropathy (FJHN; OMIM 162000) is an autosomal dominant disorder characterized by hyperuricemia and gouty arthritis due to reduced kidney excretion of uric acid and progressive renal failure. Gradual progressive interstitial renal disease, with basement membrane thickening and glomerulosclerosis resulting from fibrosis, starts in early life. In most cases of FJHN, uromodulin gene (UMOD) is responsible for the disease; however, there has been only one report of a genetically confirmed FJHN family in Korea. Here we report another Korean family with FJHN, in which three male members. a father and 2 sons.developed gout and progressive renal insufficiency. The clinical, laboratory, and radiological findings were consistent with FJHN, and renal biopsy showed chronic parenchymal damage, which can be found in FJHN but is not specific to this disease. In order to confirm the diagnosis, sequence analysis of the UMOD was performed, and a novel heterozygous missense variant (c.187T>C; p.Cys63Arg) in exon 3 was identified. We assume that this variant is likely to be the causative mutation in this family, as the variant segregated with the disease. In addition, approximately two-thirds of the known mutations lead to a cysteine amino acid change in uromodulin, and all such variants have been shown to cause UMOD-associated kidney disease. In summary, we report a Korean FJHN family with three affected members by genetic analysis of the UMOD, and provide the first report of a novel heterozygous missense mutation.
doi:10.3343/alm.2013.33.4.293
PMCID: PMC3698310  PMID: 23826568
Uromodulin; Familial juvenile hyperuricemic nephropathy; Mutation; Sequence analysis; Korea
7.  Diffusion-Weighted Magnetic Resonance Imaging for the Evaluation of Prostate Cancer: Optimal B Value at 3T 
Korean Journal of Radiology  2012;14(1):61-69.
Objective
To retrospectively determine the optimal b value of diffusion-weighted imaging (DWI) for predicting the presence of localized prostate cancer, and to evaluate the utility of DWI under different b values in differentiating between cancers and benign prostatic tissues.
Materials and Methods
Eighty patients with suspected prostate cancer underwent MRI including DWI at 3T, followed by radical prostatectomy. DWI was examined under different b values. Apparent diffusion coefficient (ADC) maps were generated by using b = 0, and other b values of 300, 700, 1000 or 2000 s/mm2. For predicting the presence of cancers, four different ADC maps were analyzed independently by two blinded readers. ADCs were measured in benign and malignant tissues.
Results
For predicting the presence of 110 prostate cancers, the sensitivity and area under the curve (AUC) for an experienced reader was significantly greater at b = 1000 (85% and 0.91) than b = 300, 700 or 2000 s/mm2 (p < 0.01). For a less-experienced reader, the AUC was significantly greater at b = 700, 1000 or 2000 than b = 300 s/mm2 (p < 0.01). Mean ADCs of the cancers in sequence from b = 300 to 2000 s/mm2 were 1.33, 1.03, 0.88 and 0.68 × 10-3 mm2/s, which were significantly lower than those of benign tissues (p < 0.001).
Conclusion
The optimal b value for 3T DWI for predicting the presence of prostate cancer may be 1000 s/mm2.
doi:10.3348/kjr.2013.14.1.61
PMCID: PMC3542304  PMID: 23323032
Diffusion-weighted MR imaging; Prostate neoplasm; Apparent diffusion coefficient; Diagnosis
8.  ERCC1 as a biomarker for bladder cancer patients likely to benefit from adjuvant chemotherapy 
BMC Cancer  2012;12:187.
Background
The role of adjuvant chemotherapy and the value of molecular biomarkers in bladder cancer have not been determined. We aimed to assess the predictive and prognostic values of excision repair cross-complementation 1 (ERCC1) in identifying appropriate patients who may potentially benefit from adjuvant chemotherapy for bladder cancer.
Methods
A retrospective analysis was performed on 93 patients with completely resected transitional cell carcinoma of the bladder. ERCC1 expression was assessed by immunohistochemistry. ERCC1 expression was analyzed in 57 patients treated with adjuvant gemcitabine plus cisplatin chemotherapy and 36 who were not treated.
Results
Among 93 patients, ERCC1 expression was positive in 54 (58.1%) and negative in 39 (41.9%). ERCC1 positivity was significantly associated with longer survival (adjusted hazard ratio for death, 0.12, 95% confidence interval [CI] 0.014-0.99; P = 0.049) in the group without adjuvant chemotherapy while ERCC1 positivity was associated with shorter survival among patients who have received adjuvant chemotherapy (adjusted hazard ratio for death, 2.64; 95% CI 1.01-6.85; P = 0.047). Therefore, clinical benefit from adjuvant chemotherapy was associated with ERCC1 negativity as measured by overall survival (test for interaction, P = 0.034) and by disease-free survival (test for interaction, P = 0.20).
Conclusions
Among patients with completely resected transitional cell carcinoma of the bladder, those with ERCC1-negative tumors seemed to benefit more from adjuvant gemcitabine plus cisplatin chemotherapy than those with ERCC1-positive tumors. Future prospective, randomized studies are warranted to confirm our findings.
doi:10.1186/1471-2407-12-187
PMCID: PMC3404914  PMID: 22616552
9.  Micropapillary Variant of Urothelial Carcinoma 
Advances in Urology  2011;2011:217153.
Micropapillary carcinoma (MPC) of urinary tract is an uncommon variant of urothelial carcinoma with significant diagnostic and prognostic implications. Though MPC shows characteristic microscopic features, there exists interobserver variability and also it needs to be differentiated from the metastasis from other organs. The prognosis is generally poor, depending on the proportion of the micropapillary component in some reports. Early cystectomy in cases with only lamina propria invasion may be indicated according to recent studies. This review outlines the general features of this entity and briefly comments on the controversies and the recent development.
doi:10.1155/2011/217153
PMCID: PMC3189456  PMID: 22007200
10.  The Role of Endorectal Magnetic Resonance Imaging in Predicting Extraprostatic Extension and Seminal Vesicle Invasion in Clinically Localized Prostate Cancer 
Korean Journal of Urology  2010;51(5):308-312.
Purpose
We aimed to assess the clinical value of endorectal magnetic resonance imaging (MRI) in predicting extraprostatic extension and seminal vesicle invasion in patients with clinically localized prostate cancer.
Materials and Methods
A total of 54 patients who underwent radical prostatectomy for clinically localized prostate cancer were retrospectively analyzed. The findings of endorectal MRI, performed at least 3 weeks after biopsy, were compared with the pathological results of radical prostatectomy specimens. The sensitivity, specificity, and accuracy of the detection of extraprostatic extension and seminal vesicle invasion were calculated.
Results
The sensitivity, specificity, and accuracy of the endorectal MRI findings were 50.0%, 82.6%, and 77.8% for the detection of extraprostatic extension, respectively, and 75.0%, 92.0%, and 90.7% for the detection of seminal vesicle invasion, respectively. The sensitivity of endorectal MRI in the detection of extraprostatic extension improved as the Gleason score increased.
Conclusions
Endorectal MRI findings demonstrated modest sensitivity for predicting extraprostatic extension, whereas specificity was relatively high. In addition, endorectal MRI showed better sensitivity for detecting high-grade tumors.
doi:10.4111/kju.2010.51.5.308
PMCID: PMC2873883  PMID: 20495692
Magnetic resonance imaging; Neoplasm staging; Prostatic neoplasms
11.  Endocardial Fibroelastosis in a 57-Year-Old Transplant Recipient 
Korean Circulation Journal  2010;40(4):204-207.
Endocardial fibroelastosis (EFE) is characterized by deposition of collagen and elastin leading to ventricular hypertrophy and diffuse endocardial thickening. Here we report (for the first time in Korea) the case of a EFE presenting with heart failure. The patient was a 57-year-old woman who had complained of dyspnea on exertion {New York Heart Association (NYHA) functional class 3} and abdominal distension at the time of hospital admission. Echocardiography showed severe diastolic dysfunction with normal systolic function. On MRI, the contrast-enhanced delayed myocardial image demonstrated hyperenhancement in the endocardium. Owing to progressive heart failure, the patient was transplanted. Histological examination of the explanted heart showed irregularly thickened endocardium with fibrosis and elastosis in the both ventricles, compatible with the diagnosis of EFE.
doi:10.4070/kcj.2010.40.4.204
PMCID: PMC2859340  PMID: 20421963
Endocardial fibroelastosis; Cardiomyopathy, restrictive; Cardiac transplantation
12.  Effect of nicotinamide on early graft failure following intraportal islet transplantation 
Experimental & Molecular Medicine  2009;41(11):782-792.
Intraportal islet transplantation (IPIT) may potentially cure Type 1 diabetes mellitus; however, graft failure in the early post-transplantation period presents a major obstacle. In this study, we tested the ability of nicotinamide to prevent early islet destruction in a syngeneic mouse model. Mice (C57BL/6) with chemically-induced diabetes received intraportal transplants of syngeneic islet tissue in various doses. Islets were cultured for 24 h in medium with or without 10 mM nicotinamide supplementation. Following IPIT, islet function was confirmed by an intraperitoneal glucose tolerance test (IPGTT) and hepatectomy. The effects of nicotinamide were evaluated by blood glucose concentration, serum monocyte chemoattractant protein-1 (MCP-1) concentration, and immunohistology at 3 h and 24 h after IPIT. Among the various islet doses, an infusion of 300 syngeneic islets treated with nicotinamide exhibited the greatest differences in glucose tolerance between recipients of treated and untreated (i.e., control) islets. One day after 300 islet equivalent (IEQ) transplantation, islets treated with nicotinamide were better granulated than the untreated islets (P = 0.01), and the recipients displayed a slight decrease in serum MCP-1 concentration, as compared to controls. After 15 days, recipients of nicotinamide-pretreated islets showed higher levels of graft function (as measured by IPGTT) than controls. The pretreatment also prolonged graft survival (> 100 days) and function; these were confirmed by partial hepatectomy, which led to the recurrence of diabetes. Pretreatment of islet grafts with nicotinamide may prevent their deterioration on the early period following IPIT in a syngeneic mouse model.
doi:10.3858/emm.2009.41.11.084
PMCID: PMC2788732  PMID: 19641379
diabetes mellitus, type 1; hepatectomy; islets of Langerhans; islets of Langerhans transplantation; niacinamide
13.  Prolonged survival of islet allografts in mice treated with rosmarinic acid and anti-CD154 antibody 
Pancreatic islet transplantation can correct the abnormal glucose metabolism of Type 1 diabetes. Although immunosuppressants greatly reduce the acute rejection rate in transplant patients, the long-term side effects can be debilitating. Therefore, researchers are seeking to develop new immunosuppressive regimens that induce maximal levels of immunosuppression with minor side effects. Rosmarinic acid (Ros A) is a secondary metabolite of certain herbs and has multiple biological activities, including anti-inflammatory effects. Here, we have investigated whether treatment of mice with a combination of Ros A and anti-CD154 monoclonal antibody (MR1) improves islet allograft survival in a murine model. After transplantation, the mice were treated with either Ros A, MR1, or both (the "double" treatment). Allograft survival was prolonged in the double-treated animals compared to animals that received only Ros A or MR1. As is the case with the single-treated animals at 15 days after transplantation, the double-treated recipients did not display a significant decrease in the expression of cytokines or the population of activated T cells. Infiltrating CD3+ T cells were reduced in the MR1- or double therapy relative to control or RosA group. However, at the same time point, double-treated graft showed fewer apoptotic cells and increased expression of insulin and glucagons, compared to the single-treatment groups. Furthermore, long-term (> 150 days) allografts that were received with double therapy exhibited larger islet clusters and contained more insulin- and glucagon-positive cells, relative to the MR1-treated grafts. In conclusion, treatment with both Ros A and MR1 has a synergistic effect in murine islet allotransplantation.
doi:10.3858/emm.2008.40.1.1
PMCID: PMC2679315  PMID: 18305392
apoptosis; CD40 ligand; graft survival; immunosuppressive agents; islets of Langerhans transplantation; rosmarinic acid
14.  Gastric Syphilis Mimicking Adenocarcinoma: A Case Report 
Journal of Korean Medical Science  2006;21(3):559-562.
Syphilis is an unexpected diagnosis in the stomach, and the reduced incidence of syphilis has made its clinical presentation less widely appreciated. We report a 43-yr-old man suffering from epigastric tenderness with an initial diagnosis of gastric carcinoma; gastric syphilis was confirmed by demonstrating spirochetes in a gastric biopsy specimen by silver impregnation. Excessive lymphoplasmacytic infiltration with diffuse thickening of gastric rugae should raise suspicion of gastric syphilis, which should be considered in the differential diagnosis of diffuse erosive gastritis and infiltrative lesions of the stomach.
doi:10.3346/jkms.2006.21.3.559
PMCID: PMC2729968  PMID: 16778406
Stomach; Syphilis; Gastritis; Treponema Pallium
15.  Promoter Methylation of E-cadherin in Hepatocellular Carcinomas and Dysplastic Nodules 
Journal of Korean Medical Science  2005;20(2):242-247.
In order to clarify the significance of E-cadherin methylation in multistep hepatocarcinogenesis, we examined the methylation status of the E-cadherin promoter region, using methylation-specific polymerase chain reaction in 64 hepatocellular carcinomas (HCCs) and 13 dysplastic nodules (DNs), and correlated these results with E-cadherin protein expression and clinicopathologic factors of HCCs. Promoter methylation was detected in 1 of 13 (7.7%) DNs, in 5 of 13 (38.5%) Edmondson and Steiner grade I HCCs, and in 27 of 51 (52.9%) grade II or III HCCs, and a significant correlation was observed between the methylation status and the stepwise progression of hepatocarcinogenesis (p=0.004). Reduced E-cadherin immunoreactivity was found in 18 of 64 (28%) HCCs, but in none of DNs. E-cadherin methylation status in HCCs was significantly correlated with microvascular invasion (p=0.02) and tumor recurrence (p=0.04), but not with reduced E-cadherin immunoreactivity. The Kaplan-Meier method showed that methylation status did not have a significant influence on the recurrence-free survival of HCC patients (p=0.15). Our results indicate that methylation of the E-cadherin promoter region is a frequent event in HCC, which may play an important role in the stepwise progression of hepatocarcinogenesis. And the promoter methylation of E-cadherin in HCC was found to be significantly correlated with microvascular invasion and recurrence.
doi:10.3346/jkms.2005.20.2.242
PMCID: PMC2808600  PMID: 15831995
Carcinoma, Hepatocellular; Dysplastic Nodule; Cadherins; DNA Methylation

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