This Month in Investigative Urology

Article Outline

• A Novel Degradable Ureteral Stent
• Novel Epigenetic Markers for Renal Cell Carcinoma
• Decreased Acetylation of Histone H3 in Renal Cell Carcinoma
• A Potential Prognostic Marker for Bladder Cancer
• Assessment of Prostate Cancer Bone Metastases
• Copyright

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A Novel Degradable Ureteral Stent 

Ureteral stents often result in patient morbidity and the potential for a “forgotten” stent. Previous attempts at developing biodegradable ureteral stents have been unsuccessful since those stents were either not biocompatible or failed to degrade in a timely fashion. Hadaschik et al (page 1161) from Vancouver, BC, Canada evaluated a new biodegradable Double-J® stent in a porcine model. The novel stent is a radiopaque composite construct comprising biodegradable copolyester components made from monomers that are used in commercially available absorbable sutures with well-established safety records. While their highly compliant outer matrix is absorbed rapidly, the inner coil of the ureteral stent disintegrates later and assures urinary drainage. Pigs were stented unilaterally with either a biodegradable stent or a standard biostable control stent. The degradable ureteral stents began to degrade at 3 weeks and by week 7 they were completely degraded. Ureteral dilatation was significantly more pronounced in the control group. The novel stent was biocompatible on histological evaluation and led to significantly fewer urinary tract infections than controls. Clinical trials will be necessary to ascertain degradation time in humans, the ease of insertion when stones are present and the response to shock wave lithotripsy.

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Novel Epigenetic Markers for Renal Cell Carcinoma 

Hypermethylation of DNA is a common molecular alteration in human neoplasia including renal cancer. Altered methylation has a role in silencing tumor suppressor genes. DNA methylation markers have been found not only in primary tumors, but also in serum, plasma and urine in a variety of cancer types. Renal cell carcinoma (RCC) may be an ideal candidate for urine and blood screening because the kidney is at the junction of the circulatory and urological systems. Dalgin et al (page 1126) from Boston, Massachusetts searched the selected DNA regions of 19 significantly down-regulated genes whose expression patterns correlated perfectly with RCC and normal kidney tissue. Methylation patterns were analyzed in DNA extracted from 38 paired RCC normal samples. Seven significantly hypermethylated regions from 6 down-regulated genes were found. The down-regulation of all genes was verified in mRNA and protein level. Overall, the detection of hypermethylation in these highly down-regulated genes suggests that assaying for methylation using cells from urine or blood could provide the basis for a viable diagnostic assay.

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Decreased Acetylation of Histone H3 in Renal Cell Carcinoma 

Recent studies suggest that alterations in the chromatin structure by histone acetylation may have an important role in the process of neoplasia. In this study Kanao et al (page 1131) from Tokyo, Japan evaluated the acetylation of histone H3 in renal cell carcinoma and the effects of a histone deacetylase inhibitor, depsipeptide, on renal cancer cell lines. The expression of acetylated histone H3 was reduced in 85.0% of RCC compared to non-neoplastic tissue. The reduced expression was related to high nuclear tumor grade and advanced pathological tumor stage. Depsipeptide inhibited the proliferations of cell lines in a time and dose dependent manner. These results suggest that reduced acetylation of histone H3 is a common alteration in a malignant phenotype of RCC. Raising the amount of acetylated histone H3 might be a therapeutic option for renal cell carcinoma.

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A Potential Prognostic Marker for Bladder Cancer 

Epigenetics refers to the mechanism of inheritance of genetic information based on gene expression levels as opposed to gene sequence (genetics). The methylation pattern of the genome is established during development and is normally maintained throughout the life of an individual. DNA methylation is a key regulator of gene transcription and genomic stability, and alterations in DNA methylation patterns are frequently detected in human tumors. The tumor suppressor gene alteration DNA methylation is closely associated with bladder tumor development, recurrence and progression. Kim et al (page 1141) from South Korea evaluated the association between RUNX3 inactivation and bladder tumors after a long-term followup study. Of 149 patients examined 118 were followed periodically and included in the final analysis. Median follow-up was 49.8 months. Methylation of the RUNX3 promoter was observed in more than 70% of tumor samples examined. RUNX3 methylation patterns correlated significantly with development of invasive tumor, tumor progression, overall survival and cancer specific survival. The methylation status of the RUNX3 promoter could constitute a promising marker for assessing the prognosis of human bladder tumors.

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Assessment of Prostate Cancer Bone Metastases 

Many patients with prostate cancer have bone metastases that appear osteoblastic on radiographs and yet these patients have an increased risk of fractures. The discrepancy between the radiological and clinical aspects of those events is not well understood. Roudier et al (page 1154) from Seattle, Washington attempted to better characterize the histopathology of bone processes in prostate cancer bone metastases. Histomorphometry was used to evaluate multisite bone biopsies in 12 patients who died with multiple bone metastases. Bone histomorphometry revealed a wide spectrum of cancer induced bone changes at different metastatic sites within individual patients, ranging from a pronounced osteodense to a resorption lesion. Osteodense lesions were largely composed of under mineralized woven bone, which increases frailty of the new bone. Interestingly, woven bone was produced by alkaline phosphatase, spindle shaped cells arising from the connective stroma surrounding tumor cells. Despite the osteoblastic nature of bone metastases in prostate cancer, the osteolytic-osteopenic bone lesions may explain the frequent fractures observed in these patients.