Variation in the number of renal arteries (RAs) constitutes the most common and clinically important renal vascular variation. In this study, the authors describe a rare case of a 58‐year‐old male with eight RAs (bilateral quadruple) as revealed by routine multidetector computed tomography angiography. All the eight RAs originated from the abdominal aorta and penetrated the renal parenchyma at the level of renal sinus. The main RAs had the intraluminal diameter larger than the diameter of the additional renal arteries (AdRAs) at the origin. All the AdRAs had a greater length than the main RAs. These aspects are particularly important in planning microsurgical procedures. Clin. Anat. 25:973–976, 2012. © 2012 Wiley Periodicals, Inc.

Bladder cancer metastasis is virtually incurable with current platinum-based chemotherapy. We used the novel COXEN informatic approach for in silico drug discovery and identified NSC-637993 and NSC-645809 (C1311), both imidazoacridinones, as agents with high-predicted activity in human bladder cancer. Because even highly effective monotherapy is unlikely to cure most patients with metastasis and NSC-645809 is undergoing clinical trials in other tumor types, we sought to develop the basis for use of C1311 in rational combination with other agents in bladder cancer. Here, we demonstrate in 40 human bladder cancer cells that the in vitro cytotoxicity profile for C1311 correlates with that of NSC-637993 and compares favorably to that of standard of care chemotherapeutics. Using genome-wide patterns of synthetic lethality of C1311 with open reading frame knockouts in budding yeast, we determined that combining C1311 with a taxane could provide mechanistically rational combinations. To determine the preclinical relevance of these yeast findings, we evaluated C1311 singly and in doublet combination with paclitaxel in human bladder cancer in the in vivo hollow fiber assay and observed efficacy. By applying COXEN to gene expression data from 40 bladder cancer cell lines and 30 human tumors with associated clinical response data to platinum-based chemotherapy, we provide evidence that signatures of C1311 sensitivity exist within nonresponders to this regimen. Coupling COXEN and yeast chemigenomics provides rational combinations with C1311 and tumor genomic signatures that can be used to select bladder cancer patients for clinical trials with this agent.

Objectives To test, in a prostate-cancer population-based database, the validity of the finding that in a single-institution series, palliative transurethral resection of prostate (TURP) is associated with an increased risk of progression. Patients and methods Using the Surveillance and End Epidemiology Registry, we identified men who had a TURP subsequent to their diagnosis of prostate cancer, from 1998 or 1999. The outcome of interest was disease progression, as defined by the initiation of androgen-deprivation therapy or procedures indicating progressive urinary obstruction. Multivariable logistic regression analysis was used to assess the adjusted odds of signal events related to disease progression adjusting for the concurrent effect of the covariates. Results There were 29 361 men with prostate cancer and 2742 (9.3%) had a TURP after the diagnosis. These men had a mean age of 75 years and were unlikely to undergo definitive primary treatment. Men receiving TURP were more likely to undergo orchidectomy than men who did not have a TURP (odds ratio 1.64; 95% confidence interval 1.03–2.60) even after adjusting for differences in cancer-directed treatment, tumour stage and grade, prostate-specific antigen level, race, and age at diagnosis. These men were also more likely to have malignant urinary obstruction (ureteric and bladder outlet) than were men who did not have TURP. Conclusion The requirement for TURP is an adverse prognostic marker even when this is adjusted for classical tumour characteristics. Although the exact reasons for this finding are unclear, consideration should be given to adjuvant treatment in patients undergoing TURP.

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In most patients, bladder cancer metastasis is incurable with current chemotherapy. To try to address this challenge, we have recently employed the novel COXEN algorithm (1) for in silico drug discovery. This approach utilized publicly available gene expression and in vitro sensitivity data for >40k compounds in NCI-60 cell line screen, from which concordant gene expression prediction models from COXEN enabled our discovery of an imidoazacridinone drug, NSC-637993, with high activity in vitro against forty bladder cancer cell lines (2). Examination of additional “hits” provided by COXEN revealed another compound in this class, C1311 (NSC-645809, Symadex) which is undergoing clinical trials in other tumor types. Our objective was to develop the foundation for use of C1311 in bladder cancer, alone and in rational combination with other clinically relevant agents. Herein, we demonstrate in a panel of 40 human bladder cancer cells that in vitro cytotoxicity profile for C1311 closely correlates that of NSC-637993 and compares favorably to that of standard of chemotherapeutics. Using genome-wide patterns of synthetic lethality of C1311 with ORF knockouts in budding yeast, we determined that combining C1311 with taxanes could provide mechanistically rational combinations for patients that have failed first line therapy with platinum based chemotherapy. To evaluate the biological relevance of these yeast findings in bladder cancer, we evaluated C1311 singly and in doublet combination with paclitaxel in the hollow fiber assay in mice, observing striking efficacy of the agents in vivo. Last, applying COXEN gene expression prediction from 40 bladder cancer cell lines to human patient tumors with known cisplatin-based chemotherapy response data (N=30) (3), we provide evidence that signatures of C1311 sensitivity exist even within patients exhibiting no change or progressive disease on standard of care agents. Taken together, these findings provide an exemplar for COXEN-based drug discovery and development, while demonstrating the utility of yeast genetics in guidance of rational combinations in vivo. Most importantly, the high activity of these agents in vitro and in vivo calls for clinical trials of these agents, while COXEN provides genomic biomarkers that may be used for patient selection. (1) Crunkhorn S. Nat Rev Drug Discov 2007;6:782-3. (2) Lee JK et al. PNAS 2007;104:13086-91. (3) Als et al. Clin Cancer Res. 2007 Aug 1;13(15 Pt 1):4407-14. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 747.