Prostate cancer is the most common cancer in men. Advanced prostate cancer spreading beyond the gland is incurable. Identifying factors that regulate the spread of tumor into the regional nodes and distant sites would guide the development of novel diagnostic, prognostic, and therapeutic targets. The aim of our study was to examine the expression and biological role of EphB4 in prostate cancer. EphB4 mRNA is expressed in 64 of 72 (89%) prostate tumor tissues assessed. EphB4 protein expression is found in the majority (41 of 62, 66%) of tumors, and 3 of 20 (15%) normal prostate tissues. Little or no expression was observed in benign prostate epithelial cell line, but EphB4 was expressed in all prostate cancer cell lines to varying degrees. EphB4 protein levels are high in the PC3 prostate cancer cell line and several folds higher in a metastatic clone of PC3 (PC3M) where overexpression was accompanied by EphB4 gene amplification. EphB4 expression is induced by loss of PTEN, p53, and induced by epidermal growth factor/epidermal growth factor receptor and insulin-like growth factor-I/insulin-like growth factor-IR. Knockdown of the EphB4 protein using EphB4 short interfering RNA or antisense oligodeoxynucleotide significantly inhibits cell growth/viability, migration, and invasion, and induces apoptosis in prostate cancer cell lines. Antisense oligodeoxynucleotide targeting EphB4 in vivo showed antitumor activity in murine human tumor xenograft model. These data show a role for EphB4 in prostate cancer and provide a rationale to study EphB4 for diagnostic, prognostic, and therapeutic applications.

Axl plays multiple roles in tumourigenesis in several cancers. Here we evaluated the expression and biological function of Axl in renal cell carcinoma (RCC). Axl expression was analysed in a tissue microarray of 174 RCC samples by immunostaining and a panel of 11 normal tumour pairs of human RCC tissues by western blot, as well as in RCC cell lines by both western blot and quantitative PCR. The effects of Axl knockdown in RCC cells on cell growth and signalling were investigated. The efficacy of a humanised Axl targeting monoclonal antibody hMAb173 was tested in histoculture and tumour xenograft. We have determined by immunohistochemistry (IHC) that Axl is expressed in 59% of RCC array samples with moderate to high in 20% but not expressed in normal kidney tissue. Western blot analysis of 11 pairs of tumour and adjacent normal tissue show high Axl expression in 73% of the tumours but not normal tissue. Axl is also expressed in RCC cell lines in which Axl knockdown reduces cell viability and PI3K/Akt signalling. The Axl antibody hMAb173 significantly induced RCC cell apoptosis in histoculture and inhibited the growth of RCC tumour in vivo by 78%. The hMAb173-treated tumours also had significantly reduced Axl protein levels, inhibited PI3K signalling, decreased proliferation, and induced apoptosis. Axl is highly expressed in RCC and critical for RCC cell survival. Targeting Axl is a potential approach for RCC treatment.

To evaluate the prognostic role of TAMs in patients affected by non-muscle invasive bladder cancer (NMIBC), undergone Trans Urethral Resection of Bladder (TURB) and Bacillus Calmette-Guerin (BCG) therapy. Data from 40 patients (36 men, 4 women), mean age 69 years (40-83 years), treated for NMIBC with TURB and BCG instillation were collected. Two different groups were considered: group with and group without bladder cancer recurrence. Correlations between immunofluorescence measured Mtot, M1 and M2 infiltration and clinicopathological parameters were evaluated using Spearman and Mann–Whitney methods. The recurrence-free survival rate was calculated using the Kaplan-Meier method. CD68 positive cells (Mtot) were observed in all specimens tested. High Mtot, M1 and M2 infiltration was observed in patients with disease recurrence, even before endovescical BCG instillation. Significant value for M2 infiltration (p = 0,042) was found calculating significativity between two group medians before BCG therapy. p = 0,072 and p = 0,180 were observed correlating median of Mtot and M1 between two groups of patients respectively. Values of p = 0,44, p = 0,23 and p = 0,64 from correlation between DFS and Mtot, M1 and M2 median in patients before endovescical BCG instillation, were calculated respectively. Comparing DFS and Mtot, M1 and M2 median in patients group after endovescical BCG instillation significant values were obtained (p = 0,020; p = 0,02; and p = 0,029 respectively). M2 tumor infiltration could be a prognostic value of recurrence in patients with NMIBC.

Ureteral injuries are uncommon and challenging. In this study we report our institutional experience with ureteral injuries. We evaluated the American Association for the Surgery of Trauma-Organ Injury Scale (AAST-OIS) for ureteral injuries as a predictor of outcomes for complexity of repair, morbidity, mortality and associated injuries. We performed a retrospective, 120-month study (January 1992 to December 2002) at an urban, level I trauma center. In the 57 patients mean hospital Admission blood pressure +/- SD was 115 +/- 25 mm Hg, mean Revised Trauma Score was 7.38 +/- 0.84 and mean Injury Severity Score was 15 +/- 1.15. The mechanism of injury was penetrating in 55 cases (96.5%), including gunshot wound in 52 (54.5%) and stab wound in 2 (5.5%), and in blunt 2 of motor vehicle accidents (3.5%). The anatomical location was the left side in 33 cases (58%), right side in 23 (40%) and bilateral in 1 (2%). The distribution of injuries was proximal in 15 cases (26%), mid in 21 (37%) and distal in 21 (37%). Associated injuries were present in 56 patients (98%). An intraoperative diagnosis was made in 44 cases (77%). Of the patients 50 (88%) required complex repairs or an adjunct procedure, including a double pigtail stent in 33 (58%), ureteroureterostomy in 20 (35%), ureteroneocystostomy with a psoas hitch in 10 (18%), external diversion in 9 (16%), suprapubic cystostomy in 8 (14%), nephrostomy in 2 (3.5%), nephrectomy in 2 (3.5%) and ligation in 2 (3.5%). Injury grade was I to V in 5 (8%), 8 (13%), 13 (22.8%), 18 (31.6%) and 13 (22.8%) cases, respectively. Overall 51 patients (89%) survived. No deaths were related to ureteral injury. Renal salvage was achieved in 49 of the 51 surviving patients (96%). Ureteral injuries are uncommon. The complexity of repair and number of associated injuries increase with AAST-OIS injury grade. Mortality increases with AAST-OIS injury grade but it is not related to the ureteral injury. Excellent results can be achieved with complex techniques of primary repair, leading to renal salvage.

Background: Radical cystectomy is the standard treatment for muscle invasive bladder cancer, however the role and appropriate extent of an associated lymphadenectomy continues to change. Methods: We performed a detailed review of the medical literature pertaining to the development and rationale for an extended lymphadenectomy in patients undergoing radical cystectomy. Results: A perspective of lymphadenectomy and an anatomic account of bladder lymphatic drainage are presented. The technique of an extended lymphadenectomy is also highlighted. Autoptic contemporary clinical data are presented to suggest that a more extensive lymphadenectomy has both prognostic and therapeutic utility. Furthermore, the stage of the primary bladder tumor, total number of lymph nodes removed, and the lymph node tumor burden are shown to be important prognostic variables in patients undergoing cystectomy with pathologic evidence of lymph node metastasis. Conclusions: Radical cystectomy provides excellent local cancer control with the Lowe’s pelvic recurrence rates and the best long-term survival. Radical cystectomy with an appropriate extended lymphadenectomy, while surgically more challenging, does not significantly increase the morbidity or mortality of the procedure. The limits of lymph node dissection are still subject to dabate and there is growing evidence that an extended lymphadenectomy provides further diagnostic and therapeutic benefit.