Hong Sup Kim

Does phosphorylation of cofilin affect the progression of human bladder cancer

BackgroundWe determined the differently expressed protein profiles and their functions in bladder cancer tissues with the aim of identifying possible target proteins and underlying molecular mechanisms for taking part in their progression.MethodsWe examined the expression of proteins by proteomic analysis and western blot in normal urothelium, non-muscle-invasive bladder cancers (NMIBCs), and muscle-invasive bladder cancers (MIBCs). The function of cofilin was analyzed using T24 human bladder cancer cells.ResultsThe expression levels of 12 proteins were altered between bladder cancers and normal bladder tissues. Of these proteins, 14-3-3σ was upregulated in both NMIBCs and MIBCs compared with controls. On the other hand, myosin regulatory light chain 2, galectin-1, lipid-binding AI, annexin V, transthyretin, CARD-inhibitor of NF-κB-activating ligand, and actin prepeptide were downregulated in cancer samples. Cofilin, an actin-depolymerizing factor, was prominent in both NMIBCs and MIBCs compared with normal bladder tissues. Furthermore, we confirmed that cofilin phosphorylation was more prominent in MIBCs than in NMIBCs using immunoblotting and immunohistochemcal analyses. Epidermal growth factor (EGF) increased the phosphorylation of cofilin and elevated the migration in T24 cells. Knockdown of cofilin expression with small interfering RNA attenuated the T24 cell migration in response to EGF.ConclusionsThese results demonstrate that the increased expression and phosphorylation of cofilin might play a role in the occurrence and invasiveness of bladder cancer. We suspected that changes in cofilin expression may participate in the progression of the bladder cancer.

Clinical implication of serum C-reactive protein in patients with uncomplicated acute pyelonephritis as marker of prolonged hospitalization and recurrence.

OBJECTIVES To analyze the clinical value of C-reactive protein (CRP) as a marker of prolonged hospitalization and a predictor of recurrence in patients after uncomplicated acute pyelonephritis (APN). METHODS A total of 202 consecutive adult patients with APN were prospectively enrolled from September 2005 to June 2007. APN was defined as the concomitant presence of 4 major and >/=2 minor clinical or laboratory signs or symptoms suggestive of APN. All patients were treated with parenteral antibiotics. The patients were discharged after normalization of body temperature, serum white blood cell counts, and urinalysis. Correlations among the recurrence of APN and various factors, including CRP, were investigated. RESULTS Of the 202 patients, 13 were excluded because of the presence of complicating factors or insufficient data. APN recurrence developed in 4 patients (2.1%). The CRP level at discharge correlated significantly with the recurrence of APN on univariate and multivariate analysis. Irrespective of the normalization of body temperature, serum white blood cell counts, and urinalysis, the recurrence of APN was significantly greater in the patients with CRP >4 mg/dL than in those with <4 mg/dL at discharge. Patients with a maximal CRP of >15 mg/dL during admission had a longer hospitalization and required more intravenous antibiotic therapy than did the patients with a maximal CRP of <15 mg/dL. CONCLUSIONS As a marker of prolonged hospitalization and recurrence, CRP can complement the present clinical and laboratory parameters used as guides in the proper treatment of patients with uncomplicated APN.

Isolation and Characterization of Smooth Muscle Cells from Rat Corpus Cavernosum Tissue for the Study of Erectile Dysfunction

Purpose Primary culture of the cavernous smooth muscle cells from corpus cavernous tissues is known to be difficult, mainly because of contamination with fibroblasts. We applied a new method for better isolation of rat penile smooth muscle cells (RPSMCs) from rat corpus cavernosum tissue for reliable ex vivo research on erectile dysfunction. Materials and Methods With the use of 8-week-old adult male Sprague-Dawley rats, ex vivo migrations of rat cavernous tissue were measured by penis and aortic ring assay by use of a Matrigel-based D-valine-modified culture method. The expression of α-smooth muscle actin (α-SMA) and platelet/endothelial cell adhesion molecule (PECAM)-1 in the RPSMCs was determined by standard immunofluorescent staining and immunoblotting. The expression patterns of phosphodiesterase (PDE) family mRNA in RPSMCs were compared with patterns in rat aortic smooth muscle cells (RASMCs) by use of quantitative real-time reverse transcription polymerase chain reaction. Results Immunocytochemical staining showed greater α-SMA-positive and PCAM-1-negative fluorescence. Moreover, whereas the expression of α-SMA was detected in the RPSMCs, that of PECAM-1 was not. The levels of PDE1A, PDE1B, PDE1C, PDE2A, PDE3A, PDE4A, PDE4B, PDE4C, PDE4D, and PDE5A mRNA in the RPSMCs were about 3.2-, 4.4-, 3.4-, 29.0-, 3.5-, 2.8-, 2.9-, 6.1-, 45.0-, and 6.0-fold the corresponding expression in RASMCs. Conclusions We developed a two-stage tissue culture method utilizing a Matrigel-based sprouting culture system to facilitate stromal cell sprouting and an adherent culture system using D-valine to eliminate the contamination of fibroblasts into the smooth muscle cells.

Prognostic Factors for Recurrence and Progression in Korean Non-Muscle-Invasive Bladder Cancer Patients: A Retrospective, Multi-Institutional Study

Purpose To identify the prognostic factors related to tumor recurrence and progression in Korean patients with non-muscle-invasive bladder cancer (NMIBC). Materials and Methods Data were collected and analyzed for 2412 NMIBC patients from 15 centers who were initially diagnosed after transurethral resection of bladder tumor (TURBT) from January 2006 to December 2010. Using univariable and multivariable Cox proportional hazards models, the prognostic value of each variable was evaluated for the time to first recurrence and progression. Results With a median follow-up duration of 37 months, 866 patients (35.9%) experienced recurrence, and 137 (5.7%) experienced progression. Patients with recurrence had a median time to the first recurrence of 10 months. Multivariable analysis conducted in all patients revealed that preoperative positive urine cytology (PUC) was independently associated with worse recurrence-free survival [RFS; hazard ratio (HR) 1.56; p<0.001], and progression-free survival (PFS; HR 1.56; p=0.037). In particular, on multivariable analysis conducted for the high-risk group (T1 tumor/high-grade Ta tumor/carcinoma in situ), preoperative PUC was an independent predictor of worse RFS (HR 1.73; p<0.001) and PFS (HR 1.96; p=0.006). On multivariable analysis in patients with T1 high-grade (T1HG) cancer (n=684), better RFS (HR 0.75; p=0.033) and PFS (HR 0.33; p<0.001) were observed in association with the administration of intravesical Bacillus Calmette-Guérin (BCG) induction therapy. Conclusion A preoperative PUC result may adversely affect RFS and PFS, particularly in high-risk NMIBC patients. Of particular note, intravesical BCG induction therapy should be administered as an adjunct to TURBT in order to improve RFS and PFS in patients with T1HG cancer.

A multi-institutional study on histopathological characteristics of surgically treated renal tumors: The importance of tumor size

Purpose The incidence of accidentally detected small renal tumors is increasing throughout the world. In this multi-institutional study performed in Korea, histopathological characteristics of contemporarily surgically removed renal tumors were reviewed with emphasis on tumor size. Materials and Methods Between January 1995 and May 2005, 1,702 patients with a mean age of 55 years underwent surgical treatment at 14 training hospitals in Korea for radiologically suspected malignant renal tumors. Clinicopathological factors and patient survival were analyzed. Results Of the 1,702 tumors, 91.7% were malignant and 8.3% were benign. The percentage of benign tumors was significantly greater among those ≤ 4 cm (13.2%) than those > 4 cm (4.5%) (p < 0.001). Among renal cell carcinoma patients, the percentage of tumors ≤ classed as stage ≥ T3 was significantly less among tumors 4 cm (5.2%) than those > 4 cm (26.8%) (p < 0.001). The percentage of tumors classed as Fuhrmans nuclear grades ≥ 3 was also significantly less among tumors ≤ 4 cm (27.3%) than tumors > 4 cm (50.9%) (p < 0.001). The 5-year cancer-specific survival rate was 82.7%, and T stage (p < 0.001), N stage (p < 0.001), M stage (p = 0.025), and Fuhrmans nuclear (p < 0.001) grade were the only independent predictors of cancer-specific survival. Conclusion In renal tumors, small tumor size is prognostic for favorable postsurgical histopathologies such as benign tumors, low T stages, and low Fuhrmans nuclear grades. Our observations are expected to facilitate urologists to adopt function-preserving approach in the planning of surgery for small renal tumors with favorable predicted outcomes.

Laparoscopic Management of Complicated Urachal Remnant in a Child

A few cases of laparoscopic surgery for urachal remnant in children has been reported in English literature. With recent developments in minimal invasive surgery, laparoscopic approach for urachal remnant in adulthood is recommended by some laparoscopic surgeons because of its technical feasibility and safety as well as cosmesis. Recently we experienced a case of complicated urachal remnant in a 14-month-old girl, who was managed by laparoscopic approach. At presentation, she complained of high fever and lower urinary tract symptoms. After 6 weeks of antibiotics therapy, laparoscopic surgery was performed transperitoneally via 3 ports. Our experience suggests that laparoscopic excision of urachal remnant can be performed easily and safely in children.

Comparison of the isolation rates and characteristics of Salmonella isolated from antibiotic-free and conventional chicken meat samples

&NA; Salmonella contamination in chicken samples can cause major health problems in humans. However, not only the effects of antibiotic treatment during growth but also the impacts of the poultry slaughter line on the prevalence of Salmonellae in final chicken meat sold to consumers are unknown. In this study, we compared the isolation rates and antimicrobial resistance of Salmonellae among antibiotic‐free, conventional, conventional Korean native retail chicken meat samples, and clonal divergence of Salmonella isolates by multilocus sequence typing. In addition, the distribution of extended‐spectrum &bgr;‐lactamase (ESBL) genes in ESBL‐producing Salmonella isolates was analyzed. A total of 72 retail chicken meat samples (n = 24 antibiotic‐free broiler [AFB] chickens, n = 24 conventional broiler [CB] chickens, and n = 24 conventional Korean native [CK] chickens) was collected from local retail markets in Seoul, South Korea. The isolation rates of Salmonellae were 66.6% in AFB chickens, 45.8% in CB chickens, and 25% in CK chickens. By analyzing the minimum inhibitory concentrations of &bgr;‐lactam antibiotics with the disc‐diffusion test, we found that 81.2% of Salmonella isolates from AFB chickens, 63.6% of isolates from CB chickens, and 50% of isolates from CK chickens were ESBL producers; all ESBL‐positive isolates had the CTX‐M‐15 genotype. Interestingly, all ESBL‐producing Salmonellae were revealed as ST16 by multilocus sequence typing and had the genetic platform of blaCTX‐M gene (IS26‐ISEcp1‐blaCTX‐M‐15‐IS903), which was first reported in Salmonellae around the world. The Salmonella ST33 strain (S. Hadar) isolated in this study has never been reported in South Korea. In conclusion, our findings showed that antibiotic‐free retail chicken meat products were also largely contaminated with ESBL‐producing Salmonellae and that their ESBL genes and genetic platforms were the same as those isolated from conventional retail chicken meat products.

Effect of Intravesical Prostatic Protrusion on the Characteristics of Lower Urinary Tract Symptom Change after 12-Week Drug Medication: A Prospective Analysis

Objectives: The aim of this study was to identify whether intravesical prostatic protrusion (IPP) is related to the characteristics of voiding symptoms improvement after drug treatment in benign prostatic hyperplasia patients.

MP43-15 BAY41-2272 ENHANCED SILDENAFIL INHIBITED MIGRATION IN RAT PENILE SMOOTH MUSCLE CELLS.

INTRODUCTION AND OBJECTIVES: In this study, we focused on whether olmesartan, an angiotensin II receptor blocker, or nifedipine, an L-type calcium channel blocker, could prevent dysfunction of NO-induced relaxation in corpus cavernosum smooth muscle in the spontaneously hypertensive rat (SHR). METHODS: Twelve-week-old male SHRs, and Wistar rats as aged-matched normotensive controls were used in this study. The treatment groups were administered olmesartan (1 or 3mg/kg, per orally (p.o.); Olm1 or Olm3, respectively) or nifedipine (30mg/kg, p.o.; Nif) for six weeks daily. Penile function was evaluated by organ bath studies with norepinephrine-induced contractions and acetylcholineinduced relaxations. Penile cGMP concentrations and mRNA levels of eNOS and nNOS were investigated. RESULTS: The SHR showed significantly increased blood pressure (BP), norepinephrine-induced hyper-contractions, acetylcholine-induced hypo-relaxations, decreased cGMP concentrations, and decreased eNOS and nNOS mRNA levels in the penile tissue. Treatment with high dose of olmesartan significantly decreased BP, significantly increased the penile cGMP concentrations, partially normalized the eNOS and nNOS mRNA levels, significantly decreased the norepinephrine-induced contractions, and normalized the acetylcholineinduced relaxation compared to the SHR. Nifedipine significantly decreased BP, increased cGMP, and normalized the hyper-contractions and hypo-relaxations observed in the SHR group, while the mRNA levels of eNOS and nNOS were significantly lower compared to the Wistar. CONCLUSIONS: Our results indicate that the dysfunction in the SHR penile tissue could be better reversed by olmesartan treatment and to a slightly lesser extent by nifedipine treatment.