Jeong Seok Hwa

Heme Oxygenase-1 Protects Rat Kidney from Ureteral Obstruction via an Antiapoptotic Pathway

This study examined the functional significance of heme oxygenase-1 (HO-1) expression on renal injury induced by ureteral obstruction in the rat kidney. Male Sprague-Dawley rats were divided into three groups, after which unilateral ureteral obstruction (UUO) was performed: untreated (group 1), treated with 30 mg/kg body wt hemin (group 2), and treated with 50 microg/kg body wt zinc (alpha) protoporphyrin eta (ZnPP) and 30 mg/kg hemin (group 3). After 7 and 14 d, histologic changes and the expression of HO-1, Bcl-2, Bad, TGF-beta, and cleaved caspase-3 were examined. Tubular lumens were dilated and epithelial cells were flattened on day 7 after UUO. Interstitial fibrosis and separation of the tubules were markedly increased on day 14. In contrast, the kidneys that were treated with hemin exhibited minimal interstitial fibrosis and flattening of epithelial cells on day 7 and fewer changes on day 14 than in the controls. However, treatment with ZnPP, an inhibitor of HO enzyme activity, eliminated the beneficial effect of hemin on interstitial fibrosis and tubular dilation. Increased HO-1 expression was associated with increased Bcl-2. In the ZnPP-treated rats, Bcl-2 signals were decreased compared with the hemin group. The level of proapoptotic Bad was not changed in any group. The positive cells for cleaved caspase-3 were significantly increased in renal tubular epithelial cells and tubulointerstitial cells in the obstructed rats, and hemin treatment decreased the caspase-3 activation. This study demonstrates that upregulation of HO-1 provides protection against renal injury that follows UUO. This effect is dependent on modulation of the antiapoptotic pathway by HO-1 expression.

Identification of Proteins Differentially Expressed in the Conventional Renal Cell Carcinoma by Proteomic Analysis

Renal cell carcinoma (RCC) is one of the most malignant tumors in urology, and due to its insidious onset patients frequently have advanced disease at the time of clinical presentation. Thus, early detection is crucial in management of RCC. To identify tumor specific proteins of RCC, we employed proteomic analysis. We prepared proteins from conventional RCC and the corresponding normal kidney tissues from seven patients with conventional RCC. The expression of proteins was determined by silver stain after two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). The overall protein expression patterns in the RCC and the normal kidney tissues were quite similar except some areas. Of 66 differentially expressed protein spots (p<0.05 by Student t-test), 8 different proteins from 11 spots were identified by MALDI-TOF-MS. The expression of the following proteins was repressed (p<0.05); aminoacylase-1, enoyl-CoA hydratase, aldehyde reductase, tropomyosin α-4 chain, agmatinase and ketohexokinase. Two proteins, vimentin and α-1 antitrypsin precursor, were dominantly expressed in RCC (p<0.05).

Spinal cord injury markedly altered protein expression patterns in the affected rat urinary bladder during healing stages.

The influence of spinal cord injury (SCI) on protein expression in the rat urinary bladder was assessed by proteomic analysis at different time intervals post-injury. After contusion SCI between T9 and T10, bladder tissues were processed by 2-DE and MALDI-TOF/MS at 6 hr to 28 days after SCI to identify proteins involved in the healing process of SCI-induced neurogenic bladder. Approximately 1,000 spots from the bladder of SCI and sham groups were visualized and identified. At one day after SCI, the expression levels of three protein were increased, and seven spots were down-regulated, including heat shock protein 27 (Hsp27) and heat shock protein 20 (Hsp20). Fifteen spots such as S100-A11 were differentially expressed seven days post-injury, and seven proteins including transgelin had altered expression patterns 28 days after injury. Of the proteins with altered expression levels, transgelin, S100-A11, Hsp27 and Hsp20 were continuously and variably expressed throughout the entire post-SCI recovery of the bladder. The identified proteins at each time point belong to eight functional categories. The altered expression patterns identified by 2-DE of transgelin and S100-A11 were verified by Western blot. Transgelin and protein S100-A11 may be candidates for protein biomarkers in the bladder healing process after SCI.

The prognostic value of immunohistochemical markers for oral tongue squamous cell carcinoma

AbstractThe objective of the study was to examine the prognostic value of hypoxia-inducible factor-1α (HIF-1α), carbonic anhydrase-IX (CA-IX), cyclooxygenase-2 (COX-2), Ki-67, and erythropoietin receptor in patients with oral tongue squamous cell carcinoma. Immunohistochemical analysis of marker expression was performed on tissue samples from 25 patients with tongue squamous cell carcinoma. The Kaplan–Meier method, univariate and multivariate analyses, and the Cox proportional hazards model were used to examine associations between patient and tumor characteristics, and the immunohistochemical results and disease-specific survival. There was no association between the expression of the five markers and disease-specific survival, and there was no statistically significant difference in the hazards ratio according to postoperative radiotherapy. There was no correlation between marker expression and prognosis. There was no association between marker expression and radioresistance or disease-specific survival. Therefore, HIF-1α, CA-IX, COX-2, Ki-67, and erythropoietin receptor are not suitable prognostic markers for tongue squamous cell carcinoma.

HIF-1α and CA-IX as predictors of locoregional control for determining the optimal treatment modality for early-stage laryngeal carcinoma.

The purpose of this study was to examine the predictive value of hypoxia‐inducible factor (HIF)−1α, carbonic anhydrase (CA)‐IX, glucose transporter (GLUT)−1, cyclooxygenase (COX)−2, Ki‐67, and erythropoietin receptor (EPOR) as immunohistochemical markers for determining the optimal treatment modality for early stage laryngeal carcinoma.

Stereotactic Body Radiation Therapy for Low- to Intermediate-risk Prostate Adenocarcinoma.

The aim of the present study was to evaluate the efficacy and toxicity of stereotactic body radiation therapy (SBRT) for low- to intermediate-risk prostate adenocarcinoma. Thirty-nine patients were retrospectively reviewed. The SBRT was delivered using the CyberKnife with the fiducial tracking method combined with In-tempo imaging. The gross target volume, which included the prostate only, was delineated on the fused CT/MRI scans. The prescription dose was delivered every other day as 5 fractions of 7.5 Gy. Venous blood was obtained before and after SBRT to assess the prostate-specific antigen (PSA) level. Toxicity was evaluated using the CTCAE, v4.03. The median follow-up time was 30.0 months. The median initial PSA level was 7.7 ng/mL. PSA levels decreased in all patients treated with SBRT, and after 5 months, the median PSA was less than 2 ng/mL. The rate of overall 3-yr actuarial biochemical failure free survival was 93.9%. Acute side effects were generally comparable with those of previous studies. The PSA change and toxicity after SBRT for low- to intermediate-risk prostate adenocarcinoma indicates favorable biochemical responses and tolerable levels of toxicity. Additionally short course treatment may produce cost benefit and convenience to patients.

Complications of Transrectal Ultrasound-Guided Prostate Biopsy: Impact of Prebiopsy Enema

Purpose Transrectal ultrasound (TRUS)-guided biopsy of the prostate is usually safe. However, some patients are hospitalized owing to complications from TRUS biopsy. We identified the risk factors for complications and effective preventive measures for treating complications after TRUS biopsy. Materials and Methods Medical records and radiological images of 1,083 patients who underwent TRUS biopsy of the prostate over 10 years in Gyeongsang National University Hospital were examined retrospectively to investigate the correlation between complications after TRUS biopsy and preventive antibiotics, prebiopsy enema, number of biopsy cores, and pathological findings. Results Complications occurred in 69 patients (6.4%). The complication rates of the 1,008 patients who received antibiotics and the 75 patients who did not were 6.3% and 8.0%, respectively (p=0.469). Complication rates of the pre-biopsy enema group (n=658) and the group without prebiopsy enema (n=425) were 4.7% and 8.9%, respectively (p=0.007). Complication rates of the 6-core biopsy group (n=41) and the 12-core biopsy group (n=955) were 7.3% and 6.3%, respectively (p=0.891). Complication rates of the prostate cancer group (n=306) and the no prostate cancer group (n=713) were 6.2% and 6.6%, respectively (p=0.740). Conclusions A prebiopsy enema was associated with a reduced risk of complications after TRUS biopsy. Preventive antibiotics, number of biopsy cores, and pathological findings did not significantly influence the complication rate.

Efficacy of Long-Term Daily Dosage of Alfuzosin 10 mg upon Sexual Function of Benign Prostatic Hypertrophy Patients: Two-Year Prospective Observational Study.

Purpose To identify sexual function improvement associated with alfuzosin (10 mg daily for 2 years). Materials and Methods We enrolled 30 men with lower urinary tract symptom (LUTS) who visited Gyeongsang National University Hospital between 2010 and 2012. At first visit, urinalysis, prostate specific antigen, transrectal ultrasound, and uroflowmetry were performed. The nternational Prostate Symptom Score (IPSS), quality of life (QoL), International Index of Erectile Function (IIEF), and Male Sexual Health Questionnaire Ejaculation Function Domain (MSHQ-EjFD) questionnaires were administered, and the subjects answered the same questionnaires at 1 month, 6 months, 1 year, and 2 years of follow-up. Results Twelve men completed of the entire study. After administration of alfuzosin, the median IPSS at first visit, 1 month, 6 months, 1 year, and 2 years was 18.00 (interquatile range [IQR]: 14.00~29.75), 20.00 (IQR: 11.50~30.00), 15.50 (IQR: 8.50~25.25), 14.50 (IQR: 9.25~19.50), and 11.50 (IQR: 5.00~17.75), respectively, which showed an improvement. The median QoL at the same times was 4.50 (IQR: 4.00~5.00), 4.50 (IQR: 4.00~5.00), 3.00 (IQR: 2.00~4.00), 3.50 (IQR: 2.25~4.00), and 3.00 (IQR: 1.00~3.00), respectively, and also showed improvement. Likewise, the median IIEF was 36.50 (IQR: 24.50~46.75), 37.50 (IQR: 26.75~47.25), 45.50 (IQR: 35.00~59.75), 48.50 (IQR: 34.75~62.75), and 47.50 (IQR: 43.25~61.00), while the median MSHQ-EjFD was 19.00 (IQR: 12.0~24.75), 19.50 (IQR: 13.50~27.75), 23.00 (IQR: 19.25~32.25), 26.50 (IQR: 18.25~34.50), 27.00 (IQR: 21.50~32.50), respectively, with both showing improvement. Conclusions After administration of alfuzosin (10 mg daily for 2 years), the IPSS, QoL, IIEF, and MSHQ-EjFD all improved significantly. This means long-term administration of 10 mg of alfuzosin daily would be effective not only for LUTS but also erectile function and ejaculation.

Relationship between serum testosterone and nocturia in men without benign prostate enlargement

Recent studies have focused on the relationship between nocturia and serum testosterone because testosterone is thought to be an important factor of prostate growth. However, it remains unclear whether altered serum concentrations of testosterone is associated with an increased risk of nocturia because patients who were taking diuretics or who had a large prostate, which may precipitate nocturia, were not excluded from most previous studies. We analyzed the clinical records of 596 non‐benign prostatic enlargement (BPE) male patients to explore the relationship between serum total testosterone and nocturia. All patients were evaluated using a serum prostate‐specific antigen (PSA) assay, measurement of serum total testosterone, transrectal ultrasonography, uroflowmetry, and a compilation of the International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF) questionnaires. Nocturia was defined as ≥2 nocturnal voiding episodes. The number of nocturia episodes was assessed using IPSS question 7. To evaluate the effect of serum testosterone on nocturia, multivariate regression analysis was performed including the covariates of age, IPSS, IIEF score, body mass index, PSA, prostate volume, and maximal urine flow rate. Based on multivariate linear analysis, serum testosterone level was not significantly associated with the severity of nocturia. However, with regard to the relationship between prevalence of nocturia and serum testosterone, prevalence of nocturia was significantly positively associated with age (OR = 1.048, p = 0.005), total IPSS (OR = 1.217, p < 0.001), and testosterone level (OR = 1.150, p = 0.041). Therefore, in men without an enlarged prostate, testosterone may play an opposing role in the etiology of nocturia.

Analysis of Motion-dependent Clinical Outcome of Tumor Tracking Stereotactic Body Radiotherapy for Prostate Cancer

Background To analyze clinical outcome of CyberKnife (CK) tumor-tracking stereotactic body radiotherapy (SBRT) for prostate cancer (Pca) according to the magnitude of intra-fractional prostate motion. Methods Medical records and daily treatment logs for 71 patients who received CK tumor-tracking SBRT were retrospectively analyzed. Statistical relationships between prostate motion and various outcome results, including local recurrence (LR), biochemical failure (BF), and treatment-related toxicity, were investigated in order to evaluate motion-dependent efficacy of tumor-tracking SBRT for Pca. Results In a total 71 patients, 3 (4.2%) patients with LR, 12 (16.9%) patients with BF, and 22 (31%) patients with grade-II or worse toxicities to rectal or bladder (22 to rectal, 22 to bladder and 8 patients to both) were observed in a median follow-up of 47 months. Magnitudes of intra-fractional tumor motion along superior-inferior, right-left, and anterior-posterior (AP) axes were 0.15 ± 0.31, 0.12 ± 0.19, and 0.73 ± 0.32 mm, respectively. Radial magnitude was estimated to be 1.0 ± 0.35 mm. Intra-fractional movement was not significantly correlated with tumor control. However, it was significant correlated with the incidence of grade-II or worse toxicity to rectum or bladder particularly when tumor motion was in the AP axis. Conclusion Our quantitative results revealed that toxicity related to SBRT treatment was highly sensitive to intra-fractional prostate movements, although local-tumor control was not affected by such movements. Our results demonstrate that precise motion correction is essential in prostate SBRT, even if it seems to be small.