Chun Il Kim

A new strategy for the diagnosis of MAGE-expressing cancers

The expression of melanoma antigen gene (MAGE), coding for tumor antigens recognized by cytotoxic T cell, is highly specific to cancer cells, but their use in the detection of a few cancer cells by reverse transcription-polymerase chain reaction (RT-PCR) has been limited by the low frequency of expression of individual MAGE genes. In order to increase MAGE detection rate in RT-PCR assay, here, we designed multiple MAGEs recognizing primers (MMRPs) that can bind to the sequences of cDNA of MAGE-1, -2, -3, -4a, -4b, -5a, -5b and-6 (MAGE 1-6) together. The nested RT-PCR assay using MMRPs, MAGE 1-6 assay, detected MAGE messages of 1 to 5 SNU484 cells in a background of 10(7) SNU638 cells. MAGE detection rate of MAGE 1-6 assay in cancers was higher than that of nested RT-PCR that detects single MAGE gene expression. The expressions of MAGE genes was detected by MAGE 1-6 assay in 70.4% (19/27) of head and neck cancer tissues, 91.7% (11/12) of breast cancer tissues, 75% (9/12) of lung cancer tissues. However, they were not detected in 18 benign lesions and 20 normal head and neck tissues and 30 blood samples from healthy donor. In conclusions, MAGE 1-6 assay can detect any cancer cells that express at least one of eight MAGE subtype genes, and this method may be very useful for the diagnosis of MAGE-expressing cancers.

Correlation between Chemokine Receptor CXCR4 Expression and Prognostic Factors in Patients with Prostate Cancer.

Purpose We evaluated the correlation between the expression of CXCR4 and prognostic factors in patients with prostate cancer. Materials and Methods A total of 57 patients who had undergone surgery for prostate cancer were enrolled. Specimens were obtained before any treatment and were stained with antihuman CXCR4 antibody. The intensity of staining was graded as low or high. The age, pretreatment prostate-specific antigen (PSA) level, Gleason score, T stage, biochemical recurrence, local recurrence, and distant metastasis were compared according to the expression of CXCR4 in patients with prostate cancer. Results Local recurrence was higher in the group with high expression, in 11 of 36 cases (30.6%), than in the group with low expression, in 1 of 21 cases (4.8%), with statistical significance (p=0.040). Distant metastasis was also associated with expression, occurring in 10 of 36 cases (27.8%) in the group with high expression and in 1 of 21 cases (4.8%) in the group with low expression (p=0.041). In the logistic regression test, CXCR4 expression was the only factor in determining local recurrence (p=0.016) and distant metastasis (0.022). Furthermore, the group with high CXCR4 expression showed significantly longer cancer-specific survival than did the low expression group (p=0.041). CXCR4 showed no association with age (p=0.881), pretreatment PSA level (p=0.584), Gleason score (p=0.640), T stage (p=0.967), or biochemical recurrence (p=0.081). Conclusions The high expression of CXCR4 was associated with local recurrence and distant metastasis. CXCR4 expression was shown to be a useful prognostic factor for patients with prostate cancer.

Cyclooxygenase-2 Overexpression in Chronic Inflammation Associated with Benign Prostatic Hyperplasia: Is It Related to Apoptosis and Angiogenesis of Prostate Cancer?

Purpose This study was performed to investigate the relationship between cyclooxygenase-2 (COX-2) expression and apoptosis/angiogenesis in inflammatory and noninflammatory benign prostatic hyperplasia (BPH) and prostate cancer (PC). Materials and Methods This study involved 64 BPH and 57 PC patients. The BPH histopathologies were classified by the presence of chronic inflammation as follows: noninflammatory BPH (NI-BPH; n=23) and inflammatory BPH (I-BPH; n=41). The association between the expression of COX-2, expression of Bcl-2, the apoptotic index (AI), expression of vascular endothelial growth factor (VEGF), and microvascular density (MVD) in the prostate was investigated. Results An overexpression of COX-2, Bcl-2, and VEGF was observed in cases of PC compared with cases of BPH. In PC, the AI was lower and MVD was higher than in BPH. In NI-BPH, I-BPH, and PC, the overexpression of COX-2, Bcl-2, and VEGF gradually increased. The AI was high in I-BPH, but did not differ significantly between the NI-BPH and I-BPH groups or between the NI-BPH and PC groups. MVD was significantly high in PC, but no significant difference was found between NI-BPH and I-BPH. A significant correlation was shown between the overexpression of COX-2 and Bcl-2, and COX-2 and VEGF. However, the AI was not correlated with the overexpression of COX-2 or Bcl-2. MVD was correlated with the overexpression of COX-2 and VEGF. Conclusions COX-2 overexpression in PC is correlated with a decrease in apoptosis and an increase in angiogenesis. Chronic inflammation in BPH causes an overexpression of COX-2, which induces the increased expression of Bcl-2 and VEGF. It is likely that chronic inflammation plays a role in the intermediate step of carcinogenesis in the prostate.

The efficacy of the EORTC scoring system and risk tables for the prediction of recurrence and progression of non-muscle-invasive bladder cancer after intravesical bacillus calmette-guerin instillation.

Purpose The European Organization for Research and Treatment of Cancer (EORTC) scoring system and risk table were introduced in the 2008 European Association of Urology guidelines on TaT1 bladder cancer. We compared the recurrence and progression rate between EORTC risk tables and authors patients who underwent transurethral resection of bladder cancer (TURB) following intravesical Bacillus Calmette-Guerin (BCG) instillation. Materials and Methods The medical records of 251 patients who underwent TURB and were diagnosed with non-muscle-invasive bladder cancer from l993 to 2007 were analyzed. The patients were divided into 2 groups: the recurrence group and the progression group. According to the EORTC scoring system, the patients in each group were categorized in terms of number of tumors, tumor size, prior recurrence rate, T category, carcinoma in situ, and pathologic grade and the scores were summed. According to the summed scores, the recurrence group and the progression group were divided into 3 subgroups: low, intermediate, and high risk, respectively. The recurrence rate and progression rate of each group were compared with the EORTC risk tables. Results The recurrence rate and progression rate were almost similar to the EORTC risk tables. However, the recurrence rate was low in the intermediate-risk group. Conclusions Clinical utilization of the EORTC scoring system and risk tables is very effective in predicting the recurrence and progression of non-muscle-invasive bladder cancer and in selecting treatment.

The Effect of Intraprostatic Chronic Inflammation on Benign Prostatic Hyperplasia Treatment

Purpose Asymptomatic chronic inflammation of the prostate is a common finding in benign prostatic hyperplasia (BPH). We investigated how the chronic inflammation affects medical treatment for BPH. Materials and Methods One pathologist reviewed the chronic inflammation of 82 BPH patients who underwent transrectal ultrasonography (TRUS)-guided needle biopsy. The extent of chronic inflammation was classified into 4 grades, categorized into two groups: the low-grade group and the high-grade group. We compared total, voiding, and storage International Prostate Symptom Score (IPSS) and quality of life (QoL) between the groups at baseline and 1, 3, 6, and 12 months after medical treatment for BPH. Results There were no significant differences in total IPSS or QoL between the groups during the follow-up period. The low-grade group showed continuous improvement of storage symptoms until 12 months; however, the high-grade group showed improvement until 3 months. Maximal improvements of QoL were observed at 6 months in the high-grade group and at 3 months in the low-grade group. There was no episode of surgery in the low-grade group, but four patients in the high-grade group (9.1%) underwent surgical treatment due to acute urinary retention or insufficient therapeutic response. Conclusions Although there was no statistical significance, improvements in IPSS were higher and lasted longer in the low-grade group. We might suggest medical treatment for intraprostatic chronic inflammation in BPH patients.

Usefulness of Preoperative Serum Testosterone as a Predictor of Extraprostatic Extension and Biochemical Recurrence

Purpose A great variety of studies on preoperative serum testosterone as a predictor of progression of prostate cancer have been reported recently. The purpose of this study was to investigate the relationship of preoperative serum testosterone levels in patients who underwent radical prostatectomy with prognostic factors. Materials and Methods Clinical data were collected from 60 patients who underwent radical prostatectomy. The 60 cases were divided into 2 groups according to their preoperative serum testosterone levels: group 1 (n=21), <3 ng/ml; group 2 (n=39), ≥3 ng/ml. The groups were compared according to prog-ression factors. Multivariate logistic regression analysis was performed to determine the correlation between biochemical recurrence and each variable. Results The incidence of extraprostatic invasions was significantly higher in group 1 with 13 cases in group 1 (61.9%) and 11 cases in group 2 (28.2%) (p=0.011). The incidence of biochemical recurrence was also significantly higher in group 1 with 5 cases in group 1 (23.8%) and 2 cases in group 2 (5.1%) (p=0.032). A low serum testosterone level (≤3 ng/ml) was associated with an increased risk of biochemical recurrence (odds ratio [OR], 13.64; 95% confidence interval [CI], 1.66 to 2.43; p=0.015) and an increased risk of extraprostatic invasions (OR, 4.96; 95% CI, 1.41 to 17.38; p=0.012). Conclusions The incidence rates of extraprostatic invasions and biochemical recurrence were significantly higher in the group with preoperative average serum testosterone of less than 3 ng/ml. Therefore, these results suggest that preoperative average serum testosterone will be useful in predicting postoperative prostate cancer progression.

Pathological upgrading in prostate cancer patients eligible for active surveillance: Does prostate-specific antigen density matter?

Purpose To evaluate prospectively the role of prostate-specific antigen (PSA) density in predicting Gleason score upgrading in prostate cancer patients eligible for active surveillance (T1/T2, biopsy Gleason score≤6, PSA≤10 ng/mL, and ≤2 positive biopsy cores). Materials and Methods Between January 2010 and November 2013, among patients who underwent greater than 10-core transrectal ultrasound-guided biopsy, 60 patients eligible for active surveillance underwent radical prostatectomy. By use of the modified Gleason criteria, the tumor grade of the surgical specimens was examined and compared with the biopsy results. Results Tumor upgrading occurred in 24 patients (40.0%). Extracapsular disease and positive surgical margins were found in 6 patients (10.0%) and 8 patients (17.30%), respectively. A statistically significant correlation between PSA density and postoperative upgrading was found (p=0.030); this was in contrast with the other studied parameters, which failed to reach significance, including PSA, prostate volume, number of biopsy cores, and number of positive cores. Tumor upgrading was also highly associated with extracapsular cancer extension (p=0.000). The estimated optimal cutoff value of PSA density was 0.13 ng/mL2, obtained by receiver operating characteristic analysis (area under the curve=0.66; p=0.020; 95% confidence interval, 0.53-0.78). Conclusions PSA density is a strong predictor of Gleason score upgrading after radical prostatectomy in patients eligible for active surveillance. Because tumor upgrading increases the potential for postoperative pathological adverse findings and prognosis, PSA density should be considered when treating and consulting patients eligible for active surveillance.

Relationship Between Spontaneous Passage Rates of Ureteral Stones Less Than 8 mm and Serum C-Reactive Protein Levels and Neutrophil Percentages

Purpose A ureter obstruction caused by a ureteral stone results in inflammatory changes in the proximal submucosal layer and prevents the spontaneous passage of the ureteral stone. Accordingly, we analyzed the relationship between the spontaneous passage rates of ureteral stones less than 8 mm in size and serum C-reactive protein (CRP) levels and neutrophil percentages. Materials and Methods A total of 187 patients who were diagnosed with ureteral stones less than 8 mm in size and were managed consecutively at Keimyung University Dongsan Medical Center from January 2001 to January 2011 were retrospectively analyzed. Ureteral stone removal was defined as no ureteral stone shown in an imaging test without any treatment for 8 weeks after diagnosis. The patients were divided into three groups according to the levels of serum CRP and into two groups according to neutrophil percentage. The associations between these factors and ureteral stone passage rates were then examined. Results The ureteral stone passage rates of the low serum CRP level group, the medium serum CRP level group, and the high serum CRP level group were 94.1% (159/169), 70% (7/10), and 50.0% (4/8), respectively. The passage rates of ureteral stones in the group with a normal neutrophil percentage and in the group with a higher neutrophil percentage were 94.5% (121/128) and 83.1% (49/59), respectively (p=0.011). Conclusions Measuring serum CRP levels and neutrophil percentages in patients with small ureteral stones of less than 8 mm is useful in predicting whether the stone will be spontaneously passed. When the serum CRP level and neutrophil percentage of a patient are high, aggressive treatment such as extracorporeal shock wave lithotripsy should be considered.

Correlation between Claudins Expression and Prognostic Factors in Prostate Cancer

Purpose The purpose of this study was to evaluate the correlation between the expression of claudins and prognostic factors in patients with prostate cancer. Materials and Methods The subjects of this study were 48 patients who had undergone surgery for prostate cancer. The Gleason score (6 or lower, 7 or higher), prostate-specific antigen (PSA) level, T stage, biochemical recurrence, local recurrence, and distant metastasis were compared according to the expression of claudin-1 and claudin-5 in prostate cancer. Results In the group with a low expression of claudin-1, the Gleason score was 7 points or higher in 18 cases (82%) and 6 points or lower in 4 cases (18%). In the group with a high expression of claudin-1, the Gleason score was 7 points or higher in 13 cases (50%) and 6 points or lower in 13 cases (50%). Thus, the low-expression group had more cases with a Gleason score of 7 or higher (p=0.022). The group with a low expression of claudin-5 also had more cases with a Gleason score of 7 or higher (p=0.011). The mean PSA values in the groups with a low and high expression of claudin-1 were 9.6 ng/ml and 5.6 ng/ml, respectively (p=0.007). A low expression of claudin-5 was also associated with a high PSA value (p=0.002). There was no statistical difference in the expression of claudin-1 and claudin-5 by T stage, biochemical recurrence, local recurrence, or distant metastasis. Conclusions The low expression of claudin-1, claudin-5 was associated with a Gleason score of 7 or higher and a high PSA value in prostate cancer.

Long-Term Effect of Loxoprofen Sodium on Nocturia in Patients with Benign Prostatic Hyperplasia

Purpose We evaluated the long-term effects of loxoprofen on nocturia in patients with benign prostatic hyperplasia (BPH). Materials and Methods Between January 2006 and December 2008, 40 BPH patients with 2 or more episodes of nocturia received an alpha-blocker, 5-alpha reductase inhibitor, and a single dose of 60 mg of loxoprofen at night before sleep for 12 months (Group I). During the same period, 38 BPH patients selected as the control group received an alpha-blocker and 5-alpha reductase inhibitor (Group II). Patients were reevaluated after 3, 6, and 12 months of treatment by the number of nocturia episodes and side effects. Results After 3 months of treatment, the number of nocturia episodes decreased significantly compared with baseline in both group I and group II (1.9±0.7, 2.1±0.7, respectively, p<0.05). The degree of decrease in nocturia was significantly different between the groups (-1.5±0.9, -1.1±0.9, respectively, p=0.034). After 6 and 12 months, the number of nocturia episodes decreased significantly compared with baseline in both group I and group II (p<0.05), but the degree of decrease was not significantly different between the groups (p>0.05). After 6 and 12 months of treatment in group I, treatment-emergent adverse events, including 5 cases of gastric discomfort (12.5%), 3 cases of leg edema (7.5%), and 1 case of decreased urine volume (2.5%), occurred in 9 of the 40 (22.5%) patients. Conclusions Loxoprofen can be an effective treatment for patients with nocturia secondary to BPH in the short term. Long-term use of loxoprofen is not recommended because of the side effects.