In transitional cell carcinoma, the most common form of bladder cancer, overexpression of the matrix metalloproteinases MMP-2 and MMP-9 offers prognostic value as markers of disease-specific survival. These molecules have been implicated in metastasis of bladder cancer, but the underlying mechanisms through which they are controlled are poorly defined. In this study, we investigated a role of p38 mitogen-activated protein kinase (MAPK) in this process, using bladder cancer cell lines HTB9 and HTB5 that were derived from different tumor stages. p38 MAPK modulated MMP-2/9 mRNA levels at the levels of transcript stability and MMP-2/9 activity along with invasive capacity. We defined a downstream effector of p38 MAPK, MAPKactivated protein kinase 2 (MAPKAPK2), that was associated with MMP-2/9 activation. Ectopic expression of wild-type or constitutively active forms of MAPKAPK2 increased MMP-2/9 activities and invasive capacity. Conversely, p38 MAPK inhibition blocked the MAPKAPK2-mediated increase in MMP-2/9 activities and the invasive capacity of the cancer cells. Our findings implicate p38 MAPK and MAPKAPK2 in mediating bladder cancer invasion via regulation of MMP-2 and MMP-9 at the level of mRNA stability. Cancer Res; 70(2); 832-41.

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 g/kg body wt zinc (␣) protoporphyrin (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-␤, 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.

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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).

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High levels of HIF-1α or CA-IX expression were significantly correlated with residual tumor after radiotherapy for early stage laryngeal carcinomas. Alternative treatment modalities to primary radiotherapy should be considered for early stage laryngeal carcinomas showing high HIF-1α or CA-IX expression.

For identification and targeting of tumor-associated marker proteins, the proteome of clear cell type of renal cell carcinoma (RCC) and normal kidney tissues was analyzed by 2-DE. Ketohexokinase (also called fructokinase), which catalyzes the phosphorylation of fructose to fructose 1-phosphate, was identified by MALDI-TOF MS and found to be expressed at low rates in the renal tumor tissues. We found a decreased amount of ketohexokinase mRNA in RCC compared to that observed in the normal kidney tissues by Northern blot. The activity of ketohexokinase in 20 clear cell RCC specimens and the 20 corresponding normal kidneys was investigated, and its activity was shown to be approximately 1.4-fold lower in the RCC specimens than in the normal kidney. Ketohexokinase activity in tumor stage pT3 RCC was 1.5-fold lower than in pT1 RCC. The level of ketohexokinase activity in histological grade 3 RCC was 1.8-fold lower than that in grade 1 cancer. In addition, using in situ hybridization, it was revealed that ketohexokinase in the normal kidney tissue was confined to the proximal tubular epithelial cells, while the expression of ketohexokinase in RCC tissues was extremely low. Our research results show that the expression of human ketohexokinase was diminished in clear cell RCC.

PurposeTransrectal 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 MethodsMedical 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.ResultsComplications 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).ConclusionsA 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.