12 research outputs found
Surgical and oncological results after rectal resections with or without previous treatment for prostate cancer
IntroductionPrevious treatment for prostate cancer (PC) may potentially affect the surgical and oncological outcomes of subsequent rectal cancer surgery, but there are only a few studies regarding this particular group. In this study, we present the 3-year surgical and oncological results of rectal cancer patients who had received previous treatment for PC at a single Finnish tertiary referral centre.Material and methodsData regarding all male patients diagnosed with rectal cancer and treated at Tampere University Hospital (TAUH) between 1997 and 2016 were gathered from medical records. In total, this study included 553 rectal cancer patients who underwent curative surgery, and 54 of them (9.8%) had a prior history of treatment for prostate cancer.ResultsPatients in the PC group were older and had more comorbidities compared with those in the non-PC group. The PC patients had a significantly higher risk of permanent stoma compared with the non-PC patients (61.5% vs. 45.2%, respectively, p = 0.025). The PC patients seemed to have lower tumours than the non-PC patients (87% vs. 75%, respectively, p = 0.05). Overall, the 3-year overall survival (OS) for the PC and non-PC patients was 74.1% and 80.6%, respectively. No significant differences were observed between the study groups even in the age-adjusted comparison [hazard ratio (HR): 1.07, confidence interval (CI) 95%: 0.60–1.89]. In the univariable analysis, radically operated patients without a history of PC exhibited an improved overall survival, (HR: 2.46, 95% CI: 1.34–4.53, p = 0.004). However, only a higher age-adjusted Charlson comorbidity index (CCI) and a low tumour location (<10 cm) were found to have an independent prognostic impact on worse OS in the multivariable analysis (HR: 1.57, 95% CI: 1.36–1.82, p < 0.001 and HR: 2.74, 95% CI: 1.32–5.70, p = 0.007, respectively). No significant differences were observed between the groups in terms of disease-free or local recurrence-free survival.ConclusionRectal cancer is more frequently found in the middle or lower part of the rectum in patients who have previously received treatment for prostate cancer. These patients also have a higher likelihood of requiring a permanent stoma. In radically operated rectal cancer, the PC group had a worse OS rate, according to the univariable analysis. However, the only independent prognostic factors for a worse OS that were highlighted in the multivariable analysis included a higher CCI and a low tumour location
Conserved BK Channel-Protein Interactions Reveal Signals Relevant to Cell Death and Survival
The large-conductance Ca2+-activated K+ (BK) channel and its β-subunit underlie tuning in non-mammalian sensory or hair cells, whereas in mammals its function is less clear. To gain insights into species differences and to reveal putative BK functions, we undertook a systems analysis of BK and BK-Associated Proteins (BKAPS) in the chicken cochlea and compared these results to other species. We identified 110 putative partners from cytoplasmic and membrane/cytoskeletal fractions, using a combination of coimmunoprecipitation, 2-D gel, and LC-MS/MS. Partners included 14-3-3γ, valosin-containing protein (VCP), stathmin (STMN), cortactin (CTTN), and prohibitin (PHB), of which 16 partners were verified by reciprocal coimmunoprecipitation. Bioinformatics revealed binary partners, the resultant interactome, subcellular localization, and cellular processes. The interactome contained 193 proteins involved in 190 binary interactions in subcellular compartments such as the ER, mitochondria, and nucleus. Comparisons with mice showed shared hub proteins that included N-methyl-D-aspartate receptor (NMDAR) and ATP-synthase. Ortholog analyses across six species revealed conserved interactions involving apoptosis, Ca2+ binding, and trafficking, in chicks, mice, and humans. Functional studies using recombinant BK and RNAi in a heterologous expression system revealed that proteins important to cell death/survival, such as annexinA5, γ-actin, lamin, superoxide dismutase, and VCP, caused a decrease in BK expression. This revelation led to an examination of specific kinases and their effectors relevant to cell viability. Sequence analyses of the BK C-terminus across 10 species showed putative binding sites for 14-3-3, RAC-α serine/threonine-protein kinase 1 (Akt), glycogen synthase kinase-3β (GSK3β) and phosphoinositide-dependent kinase-1 (PDK1). Knockdown of 14-3-3 and Akt caused an increase in BK expression, whereas silencing of GSK3β and PDK1 had the opposite effect. This comparative systems approach suggests conservation in BK function across different species in addition to novel functions that may include the initiation of signals relevant to cell death/survival
Prostate cancer-specific survival among warfarin users in the Finnish Randomized Study of Screening for Prostate Cancer
Therapeutic antibodies targeting angiomotin inhibit angiogenesis in vivo
We have previously shown that angiomotin (Amot) mediates angiostatin inhibition of endothelial migration and tube formation in vitro. A crucial role of angiomotin in regulating endothelial cell motility is indicated by the findings that knockdown of Amot in zebrafish reduces the number of filopodia of endothelial tip cells and severely impairs the migration of intersegmental vessels. In addition, targeting angiomotin using DNA vaccination inhibits angiogenesis and tumor growth in vivo. In this report, we have generated antibodies that, similar to angiostatin, bind to angiomotin on the endothelial cell surface. These antibodies inhibited FGF-2 and vascular endothelial growth factor (VEGF) -induced endothelial migration in the Boyden chamber assay. Furthermore, the anti-Amot B06 antibody significantly reduced the number of endothelial filopodia and inhibited vessel migration during retinal angiogenesis in vivo. We also show that systemic or local treatment with this antibody inhibits pathological blood vessel formation associated with tumor growth or laser-induced choroid neovascularization of the eye. These findings provide a rationale for using angiomotin antibodies for specifically targeting endothelial migration in angiogenesis-dependent diseases