Association of tumor size, location, R.E.N.A.L., PADUA and centrality index score with perioperative outcomes and postoperative renal function.

PURPOSE: Multiple scoring systems have been proposed to standardize the description of anatomical features of renal tumors. However, it remains unclear which of these systems, if any, is most useful, or whether any performs better than simply reporting tumor size or location in patients undergoing partial nephrectomy. To clarify these issues we evaluated the association of tumor size, location, R.E.N.A.L. (Radius/Exophytic/Nearness to collecting system/Anterior/Location), PADUA (Preoperative Aspects and Dimensions Used for an Anatomical classification) and centrality index scores with perioperative outcomes. MATERIALS AND METHODS: Patients undergoing partial nephrectomy with available preoperative imaging were identified from 2005 to 2011. R.E.N.A.L., PADUA and centrality index scores were assigned according to the described protocols for those systems. Associations between each variable and ischemia time, estimated blood loss, total operative time and change in estimated glomerular filtration rate were examined. RESULTS: A total of 162 patients were identified with a median tumor size of 3.1 cm (IQR 2.2 to 4.6). Median estimated blood loss, ischemia time and total operative time were 200 ml (IQR 100 to 300), 24 minutes (IQR 20 to 30) and 211 minutes (IQR 179 to 249), respectively. Each scoring system was found to have a statistically significant (p <0.001) correlation with ischemia time, with the centrality index system showing the strongest correlation. Furthermore, each of the scoring systems showed a stronger correlation with ischemia time than tumor size or tumor location. CONCLUSIONS: Each scoring system outperformed tumor size and location, and may be useful when describing the surgical complexity of renal tumors treated with partial nephrectomy.

Dysfunctional transforming growth factor-beta receptor II accelerates prostate tumorigenesis in the TRAMP mouse model.

The contribution of a dysfunctional transforming growth factor-beta type II receptor (TGF beta RII) to prostate cancer initiation and progression was investigated in an in vivo mouse model. Transgenic mice harboring the dominant-negative mutant TGF-beta type II receptor (DNTGF beta RII) in mouse epithelial cell were crossed with the TRAMP prostate cancer transgenic mouse to characterize the in vivo consequences of inactivated TGF-beta signaling on prostate tumor initiation and progression. Histopathologic diagnosis of prostate specimens from the TRAMP+/DNTGF beta RII double transgenic mice revealed the appearance of early malignant changes and subsequently highly aggressive prostate tumors at a younger age, compared with littermates TRAMP+/Wt TGF beta RII mice. Immunohistochemical and Western blotting analysis revealed significantly increased proliferative and apoptotic activities, as well as vascularity and macrophage infiltration that correlated with an elevated vascular endothelial growth factor and MCP-1 protein levels in prostates from TRAMP+/DNTGF beta RII+ mice. An epithelial-mesenchymal transition (EMT) effect was also detected in prostates of TRAMP+/DNTGF beta RII mice, as documented by the loss of epithelial markers (E-cadherin and beta-catenin) and up-regulation of mesenchymal markers (N-cadherin) and EMT-transcription factor Snail. A significant increase in the androgen receptor mRNA and protein levels was associated with the early onset of prostate tumorigenesis in TRAMP+/DNTGF beta RII mice. Our results indicate that in vivo disruption of TGF-beta signaling accelerates the pathologic malignant changes in the prostate by altering the kinetics of prostate growth and inducing EMT. The study also suggests that a dysfunctional TGF beta RII augments androgen receptor expression and promotes inflammation in early stage tumor growth, thus conferring a significant contribution by TGF-beta to prostate cancer progression.

Intracellular death platform steps-in: targeting prostate tumors via endoplasmic reticulum (ER) apoptosis.

Molecular targeting of apoptotic signaling pathways has been extensively studied in recent years and directed towards the development of effective therapeutic modalities for treating advanced androgen-independent prostate tumors. The majority of therapeutic agents act through intrinsic or mitochondrial pathways to induce programmed cell death. The induction of apoptosis through endoplasmic reticulum (ER) stress pathways may provide an alternative to treat patients. The functional interaction between the BCL-2 family members and regulation of calcium homeostasis in the ER provides a critical link to the life or death outcome of the cell. Apoptosis induction mediated by ER stress-inducing agents is just beginning to be exploited for therapeutic targeting of prostate tumors. Insightful dissection of recently discovered apoptotic signaling pathways that function through the endoplasmic reticulum may identify novel molecules that could effectively target both androgen-dependent and androgen-independent prostate tumors. In this review, we focus on linking ER stress-induced apoptosis to therapeutic targeting of prostate tumors and dissect its cross-talk with the intrinsic and extrinsic apoptotic pathways.