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Purpose To assess the outcome of prostate cancer (PCa) patients diagnosed with oligometastatic disease at recurrence and treated with stereotactic body radiotherapy (SBRT). Methods Non-castrate patients with up to 3 synchronous metastases (bone and/or lymph nodes) diagnosed on positron emission tomography - computed tomography, following biochemical recurrence after local curative treatment, were treated with (repeated) SBRT to a dose of 50 Gy in 10 fractions or 30 Gy in 3 fractions. Androgen deprivation therapy-free survival (ADTFS) defined as the time interval between the first day of SBRT and the initiation of ADT was the primary endpoint. ADT was initiated if more than 3 metastases were detected during follow-up even when patients were still asymptomatic. Secondary endpoints were local control, progression free survival (PFS) and toxicity. Toxicity was scored using the Common Terminology Criteria for Adverse Events. Results With a median follow-up from time of SBRT of 2 years, we treated 50 patients with 70 metastatic lesions with a local control rate of 100%. The primary involved metastatic sites were lymph nodes (54%), bone (44%), and viscera (2%). The median PFS was 19 mo (95% CI: 13-25 mo) with 75% of recurring patients having ⩽3 metastases. A 2nd and 3rd course of SBRT was delivered in 19 and 6 patients respectively. This results in a median ADT-FS of 25 months (20-30 mo). On univariate analysis, only a short PSA doubling time was a significant predictor for both PFS (HR: 0.90, 95%CI: 0.82 - 0.99) and ADT-FS (HR: 0.83; 95%CI: 0.71 - 0.97). Ten patients (20%) developed toxicity following treatment, which was classified as grade I in 7 and grade II in 3 patients. Conclusion Repeated SBRT for oligometastatic prostate cancer postpones palliative androgen deprivation therapy with 2 years without grade III toxicity. [ABSTRACT FROM AUTHOR]

Inflammatory bowel diseases ( IBDs) are recurrent intestinal pathologies characterized by a compromised epithelial barrier and an exaggerated immune activation. Mediators of immune cell infiltration may represent new therapeutic opportunities. Metallothioneins ( MTs) are stress-responsive proteins with immune-modulating functions. Metallothioneins have been linked to IBDs, but their role in intestinal inflammation is inconclusive. We investigated MT expression in colonic biopsies from IBDs and acute infectious colitis patients and healthy controls and evaluated MT's role in experimental colitis using MT knockout mice and anti- MT antibodies. Antibody potential to target extracellular MT and its mechanism was tested in vitro. Biopsies of patients with active colitis showed infiltration of MT-positive cells in a pattern that correlated with the grade of inflammation. MT knockout mice displayed less severe acute dextran sulphate sodium ( DSS)-induced colitis compared to congenic wild-type mice based on survival, weight loss, colon length, histological inflammation and leukocyte infiltration. Chronic DSS-colitis confirmed that Mt1 and Mt2 gene disruption enhances clinical outcome. Blockade of extracellular MT with antibodies reduced F4/80-positive macrophage infiltration in DSS- and trinitrobenzene sulphonic acid-colitis, with a tendency towards a better outcome. Whole-body single-photon emission computer tomography of mice injected with radioactive anti- MT antibodies showed antibody accumulation in the colon during colitis and clearance during recovery. Necrotic and not apoptotic cell death resulted in western blot MT detection in HT29 cell supernatant. In a Boyden chamber migration assay, leukocyte attraction towards the necrotic cell supernatant could be abolished with anti- MT antibody, indicating the chemotactic potential of endogenous released MT. Our results show that human colitis is associated with infiltration of MT-positive inflammatory cells. Since antibody blockade of extracellular MT can reduce colitis in mice, MT may act as a danger signal and may represent a novel target for reducing leukocyte infiltration and inflammation in IBD patients. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd [ABSTRACT FROM AUTHOR]

Objectives. Loading of biological matrices offers an opportunity to induce specific cell behaviour. We previously reported the use of growth factors to promote cell invasion and proliferation in tissue valve engineering. We investigated biological matrices preloaded with heparin as an ionically attractive template for the binding, activation and sustained release of basic fibroblast growth factor (bFGF). Methods. Heparin loading concentrations were evaluated and different incubation times were tested. Heparin and heparin-bound bFGF uptake and release were evaluated by 123I radio-labelling. Biological activity of bFGF was evaluated in vitro. Results. Maximum heparin uptake was observed for 2000 μg/ml at 2 h and stabilized thereafter. bFGF-loaded matrices showed an initial burst release of 15% within 4 h and thereafter sustained release reaching 21% at 24 h. Released bFGF was bioactive. Conclusions. This model would be useful in tissue engineering using porcine aortic matrices and could be applied using other growth factors or combinations. [ABSTRACT FROM AUTHOR]

We compared fluor-18 choline positron emission tomography/computed tomography (PET/CT) and axial skeleton magnetic resonance imaging (MRI) prospectively obtained for the detection of bone metastases in non-castrated patients with biochemically recurrent prostate cancer following primary treatment. PET/CT was performed 45 min post-injection of 3-4 MBq/kg F-18 methyl choline. MRI included T1- and fluid sensitive T2-weighted images of the spine and pelvis. Readers were initially blinded from other results and all scans underwent independent double reading. The best valuable comparator (BVC) defined the metastatic status. On the basis of the BVC, 15 out of 64 patients presented with 24 bone metastases. On a patient level, the sensitivity and specificity of MRI and PET were not significantly different. On a lesion level, the sensitivity of MRI was significantly better compared to PET, and the specificity did not differ significantly. In conclusion, axial MRI is an interesting screening tool for the detection of bone metastases because of its low probability of false negative results. However, F-18 choline PET is a valuable addition as it can overrule false positive MRI results and detect non-axial metastases., Competing Interests: The authors declare no conflict of interest