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Objective: To test the hypothesis that FYN, a member of the SRC family of kinases (SFKs), is up-regulated in prostate cancer, as FYN is functionally distinct from other SFKs, and interacts with FAK and paxillin (PXN), regulators of cell morphology and motility., Materials and Methods: Through data-mining in Oncomine (http://www.oncomine.org), cell-line profiling with immunoblotting, quantitative reverse transcription and polymerase chain reaction (RT-PCR) and immunohistochemical analysis, we described FYN expression in prostate cancer. The analysis included 32 cases of prostate cancer, nine of prostatic intraepithelial neoplasia (PIN) and 19 normal prostates. Samples were scored for the percentage of stained glands and intensity of staining (from 0 to 3). Each sample was assigned a composite score generated by multiplying percentage and intensity., Results: Data-mining showed an eight times greater FYN expression in prostate cancer than in normal tissue; this was specific to FYN and not present for other SFKs. Expression of FYN in prostate cancer cell lines (LNCaP, 22Rv1, PC3, DuPro) was detected using quantitative RT-PCR and immunoblotting. Expression of FYN and its signalling partners FAK and PXN was detected in human tissue. Comparing normal with cancer samples, there was a 2.1-fold increase in median composite score for FYN (P < 0.001) 1.7-fold increase in FAK (P < 0.001), and a doubling in PXN (P < 0.05). There was a 1.7-fold increase in FYN (P < 0.05) and a 1.6-fold increase in FAK (P < 0.01) in cancer compared with PIN., Conclusions: These studies support the hypothesis that FYN and its related signalling partners are up-regulated in prostate cancer, and support further investigation into the role of the FYN as a therapeutic target.

Objective: To assess, in a pilot study, the feasibility of delivering a microparticulate ice slurry (MPS) to provide regional hypothermia, as renal cooling during laparoscopic procedures is cumbersome and inefficient., Materials and Methods: An ex vivo preparation was used to simulate the boundary conditions of a kidney. Four pig kidneys were placed onto a thin membrane overlying a constant temperature bath (37 degrees C) with parenchymal thermocouples. Renal surfaces were coated with MPS and temperatures recorded. In an in vivo pig model we assessed laparoscopic delivery and cooling ability of the MPS under physiological conditions. Kidneys in two pigs were laparoscopically exposed; thermocouple probes were placed throughout the kidney and the hilum was clamped. MPS was delivered through a modified 5-mm laparoscopic suction/irrigation cannula. Cortical and core body temperatures were measured., Results: In the ex vivo study, the mean (sd) initial temperature was 37.1 (0.4) degrees C; the mean time to reach 15 degrees C was 10.3 (2.6) min and the mean nadir temperature was 13.0 (1.5) degrees C. In vivo, the MPS was delivered with no technical difficulty; the mean renal unit starting temperature and core body temperature were 37.2 degrees C and 37.0 degrees C, respectively. The mean (range) time to reach 15 degrees C was 16.5 (5.5-28.6) min. The mean nadir core body temperature was 34.0 degrees C., Conclusion: This initial study showed efficient and rapid induction of renal hypothermia using MPS delivered through 5-mm laparoscopic ports, with no technical difficulty. These exploratory pilot findings support further, larger scale, histopathological and renal functional investigations of topical ice slurries as a means of providing renal hypothermia in laparoscopic procedures.