Targeting HOX transcription factors in prostate cancer

YesBackground: The HOX genes are a family of transcription factors that help to determine cell and tissue identity during early development, and which are also over-expressed in a number of malignancies where they have been shown to promote cell proliferation and survival. The purpose of this study was to evaluate the expression of HOX genes in prostate cancer and to establish whether prostate cancer cells are sensitive to killing by HXR9, an inhibitor of HOX function. Methods: HOX function was inhibited using the HXR9 peptide. HOX gene expression was assessed by RNA extraction from cells or tissues followed by quantitative PCR, and siRNA was used to block the expression of the HOX target gene, cFos. In vivo modelling involved a mouse flank tumour induced by inoculation with LNCaP cells. Results: In this study we show that the expression of HOX genes in prostate tumours is greatly increased with respect to normal prostate tissue. Targeting the interaction between HOX proteins and their PBX cofactor induces apoptosis in the prostate cancer derived cell lines PC3, DU145 and LNCaP, through a mechanism that involves a rapid increase in the expression of cFos, an oncogenic transcription factor. Furthermore, disrupting HOX/PBX binding using the HXR9 antagonist blocks the growth of LNCaP tumours in a xenograft model over an extended period. Conclusion: Many HOX genes are highly over-expressed in prostate cancer, and prostate cancer cells are sensitive to killing by HXR9 both in vitro and in vivo. The HOX genes are therefore a potential therapeutic target in prostate cancer.The authors gratefully acknowledge the support of the Prostate Project charity (UK)

Changes in neuronal activation patterns in response to androgen deprivation therapy: a pilot study

<p>Abstract</p> <p>Background</p> <p>A common treatment option for men with prostate cancer is androgen deprivation therapy (ADT). However, men undergoing ADT may experience physical side effects, changes in quality of life and sometimes psychiatric and cognitive side effects.</p> <p>Methods</p> <p>In this study, hormone naïve patients without evidence of metastases with a rising PSA were treated with nine months of ADT. Functional magnetic resonance imaging (fMRI) of the brain during three visuospatial tasks was performed at baseline prior to treatment and after nine months of ADT in five subjects. Seven healthy control patients, underwent neuroimaging at the same time intervals.</p> <p>Results</p> <p>ADT patients showed reduced, task-related BOLD-fMRI activation during treatment that was not observed in control subjects. Reduction in activation in right parietal-occipital regions from baseline was observed during recall of the spatial location of objects and mental rotation.</p> <p>Conclusions</p> <p>Findings, while preliminary, suggest that ADT reduces task-related neural activation in brain regions that are involved in mental rotation and accurate recall of spatial information.</p

Mini-Flank Supra-12th Rib Incision for Open Partial Nephrectomy Compared with Laparoscopic Partial Nephrectomy and Traditional Open Partial Nephrectomy

PURPOSE: The purpose of this study was to report our approach of partial nephrectomy (PN) using a supra-12th rib mini-flank incision. We compared mini-incision open partial nephrectomy (MI-OPN) with open partial nephrectomy (OPN) and laparoscopic partial nephrectomy (LPN) to verify whether MI-OPN can be an alternative to OPN and LPN. METHODS: This was a retrospective single-center study including 194 patients who underwent partial nephrectomy (PN) between February 2005 and December 2010. Demographic, perioperative, and complication data were compared among the MI-OPN group, OPN group and LPN group. RESULTS: No statistical differences were reported in either group for age, sex, BMI, tumour side (right or left kidney), RENAL nephrometry scores, PADUA score and preoperative eGFR. The operative time was longer in LPN group when compared with MI-OPN and OPN group (all P<0.001). The warm ischemia time of LPN group was longer than MI-OPN group (P = 0.032) and OPN group (P = 0.005). The length of stay of LPN group was shorter than OPN group (P = 0.018), but was similar to MI-OPN group (P = 0.094). The incidence of renal artery clamping was lower in OPN group when compared with MI-OPN and LPN group (all P<0.001). More estimated blood loss was found in OPN group when compared with MI-OPN group (p = 0.003) and LPN group (P = 0.014). The overall incidence of postoperative complications was similar. CONCLUSIONS: The approach of MI-OPN can couple the benefits of both minimally invasive and open partial nephrectomy techniques with less estimated blood loss, shorter operative time, shorter length of stay, less postoperative complications, and a smaller incision. MI-OPN may be an effective alternative to laparoscopic or traditional open approaches, which maybe more suitable for the tumors with high RENAL nephrometry score or PADUA score