The translational potential of microRNAs as biofluid markers of urological tumours

MicroRNAs (miRNAs) are secreted by cells in vesicles, bound in a ribonucleoprotein complex or as free molecules. These miRNA secretion pathways are dysregulated in cancer, making miRNAs attractive candidate molecules for liquid biopsies. A number of studies have investigated the regulation of miRNA secretion into blood and urine and suggested that miRNAs are noninvasive diagnostic, prognostic and surveillance markers in urological carcinomas, and research in this area has increased over the past 5 years. However, methodological and analytical pitfalls exist and require addressing to enable future translation of the laboratory findings regarding miRNAs as biomarkers into clinical practice in bladder cancer, kidney cancer, prostate cancer and testicular cancer

Modifying the product distribution of a reaction within the controlled microenvironment of a colloidosome

A water-soluble colloidosome composed of PGMA–PS latex was used as a microcapsule to host a catalyzed oxidation reaction within its dodecane core. When compared to a control reaction a significant colloidosome effect was observed. Specifically, a 233% increase in the relative yield of all products was observed for the colloidosome reaction. Furthermore, when the product distributions were calculated it was evident that a switch in selectivity had taken place. These studies showed there is a significant reduction in the relative yield of the epoxide product compared to the remaining oxidation products. Additional control experiments confirmed that rate enhancements were not simply a result of concentration and that reactions were not occurring in the outer latex phase. As a consequence of these control experiments, we suggest that the colloidosome enhancement and shift in product distribution, comes about from differences in electronic environment at or close to the interface between the internal oil phase and the outer colloidal particles. This environment is able to stabilize any specific intermediates and or transition states leading to enhanced reactions for these products and higher relative yields

The miRNA-kallikrein axis of interaction: a new dimension in the pathogenesis of prostate cancer

Kallikrein-related peptidases (KLKs) are a family of serine proteases that were shown to be useful cancer biomarkers. KLKs have been shown to be dysregulated in prostate cancer (PCa). microRNAs (miRNAs) are short RNA nucleotides that negatively regulate gene expression and have been reportedly dysregulated in PCa. We compiled a comprehensive list of 55 miRNAs that are differentially expressed in PCa from previous microarray analysis and published literature. Target prediction analyses showed that 29 of these miRNAs are predicted to target 10 KLKs. Eight of these miRNAs were predicted to target more than one KLK. Quantitative real-time (qRT)-PCR demonstrated that there was an inverse correlation pattern in the expression (normal vs. cancer) between dysregulated miRNAs and their target KLKs. In addition, we experientially validated the miRNA-KLK interaction by transfecting miR-331-3p and miR-143 into a PCa cell line. Decreased expression of targets KLK4 and KLK10, respectively, and decreased cellular growth were observed. In addition to KLKs, dysregulated miRNAs were predicted to target other genes involved in the pathogenesis of PCa. These data show that miRNAs can contribute to KLK regulation in PCa. The miRNA-KLK axis of interaction projects a new element in the pathogenesis of PCa that may have therapeutic implications

Establishment of kidney cancer organoid cultures

This protocol describes an efficient novel method for cultivating kidney cancer organoids, derived directly from human clear cell renal cell carcinomas (ccRCC) or sorted cancer stem cells. The organoids recapitulate tumor-specific characteristics and display inter-tumor heterogeneity. Here we explain how to establish the organoid cultures, maintain them in defined, serum-free medium and use them for patient-specific drug testing. Within 10-14 days, a patient-derived organoid culture is established and can be serially passaged. Compared to other protocols focusing on organoid cultures derived from pediatric kidney malignancies or healthy kidneys, the protocol described here is optimized for adult ccRCC organoid cultures. Organoids established using this protocol can be used to further investigate tumor biology in a complex 3D in vitro system, complement current preclinical model-based drug studies, and advance the development of personalized therapy design

Universal Negative Poisson Ratio of Self Avoiding Fixed Connectivity Membranes

We determine the Poisson ratio of self-avoiding fixed-connectivity membranes, modeled as impenetrable plaquettes, to be sigma=-0.37(6), in statistical agreement with the Poisson ratio of phantom fixed-connectivity membranes sigma=-0.32(4). Together with the equality of critical exponents, this result implies a unique universality class for fixed-connectivity membranes. Our findings thus establish that physical fixed-connectivity membranes provide a wide class of auxetic (negative Poisson ratio) materials with significant potential applications in materials science.Comment: 4 pages, 3 figures, LaTeX (revtex) Published version - title changed, one figure improved and one reference change

Dynamics at a smeared phase transition

We investigate the effects of rare regions on the dynamics of Ising magnets with planar defects, i.e., disorder perfectly correlated in two dimensions. In these systems, the magnetic phase transition is smeared because static long-range order can develop on isolated rare regions. We first study an infinite-range model by numerically solving local dynamic mean-field equations. Then we use extremal statistics and scaling arguments to discuss the dynamics beyond mean-field theory. In the tail region of the smeared transition the dynamics is even slower than in a conventional Griffiths phase: the spin autocorrelation function decays like a stretched exponential at intermediate times before approaching the exponentially small equilibrium value following a power law at late times.Comment: 10 pages, 8eps figures included, final version as publishe

A Retrospective Multicenter Analysis of the Incidence of Bone-Only Disease at PSMA PET/CT in Castration Resistant Prostate Cancer Patients

PSMA PET/CT has unprecedented accuracy for localization of initial or recurrent prostate cancer (PC), which can be applied in a metastasis-directed therapy approach. PSMA PET/CT (PET) also has a role in the selection of patients for metastasis-directed therapy or radioligand therapy and therapy assessment in CRPC patients. The purpose of this multicenter retrospective study was to determine the incidence of bone-only metastasis in CRPC patients who underwent PSMA PET/CT for restaging, as well as identifying potential predictors of bone-only PET positivity. The study analyzed data from 179 patients from two centers in Essen and Bologna. Results showed that 20.1% of the patients had PSMA uptake only in the bone, with the most frequent lesions located in the vertebrae, ribs, and hip bone. Half half of the patients showed oligo disease in bone and may benefit from a bone-metastasis-directed therapy. Initial positive nodal status and solitary ADT were shown to be negative predictors of osseous metastasis. The role of PSMA PET/TC in this patient population needs to be further explored in terms of its role in the evaluation and adoption of bone-specific therapies

Total oxidation of propene at low temperature over Co3O4-CeO2 mixed oxides: Role of surface oxygen vacancies and bulk oxygen mobility in the catalytic activity

Co3O4, CeO2 and Co3O4\u2013CeO2 mixed oxides with Co/Ce nominal atomic ratio 0.1:5, prepared by coprecipitation method with sodium carbonate, were tested in the oxidation of propene under lean condition and the catalyst stability was checked by performing three consecutive heating\u2013cooling cycles. Characterization of the textural properties were performed by surface area measurement BET, X-ray diffraction (XRD) and scanning electron microscopy (SEM) measurements. Among the Co3O4\u2013CeO2 mixed oxides, Co3O4 (30 wt%)\u2013CeO2 (70 wt%) gives the best activity attaining full propene conversion at 250 \ub0C. This sample is characterized by the presence of Co3O4 particles well dispersed and in good contact with ceria according to BET and XRD data and as evidenced by SEM micrographs. Oxygen temperature-programmed desorption (O2 -TPD) and C3H6 -temperature-programmed reduction (C3H6-TPR) experiments were carried out in order to study the surface and bulk oxygen mobility and to correlate it to the activity. At temperature around 200 \ub0C, O2-TPD experiments showed the desorption of mobile surface oxygen species for the most active samples, Co3O4 and Co3O4 (30 wt%)\u2013 CeO2 (70 wt%). C3H6-TPR experiments for both of the oxides also evidenced a high reactivity at low temperature, especially, for Co3O4 (30 wt%)\u2013 CeO2 (70 wt%) giving at 345 \ub0C an intense peak of CO2 formation. Conversely, the ceria sample showed by C3H6-TPR much less pronounced oxygen bulk mobility, starting to react with propene above 500 \ub0C and forming only CO. In this case, the catalytic activity of ceria was explained in terms of formation of surface oxygen vacancies which are relevant to the propene oxidation in presence of gaseous oxygen

Inhibiting WNT and NOTCH in renal cancer stem cells and the implications for human patients

Current treatments for clear cell renal cell cancer (ccRCC) are insufficient because two-thirds of patients with metastases progress within two years. Here we report the identification and characterization of a cancer stem cell (CSC) population in ccRCC. CSCs are quantitatively correlated with tumor aggressiveness and metastasis. Transcriptional profiling and single cell sequencing reveal that these CSCs exhibit an activation of WNT and NOTCH signaling. A significant obstacle to the development of rational treatments has been the discrepancy between model systems and the in vivo situation of patients. To address this, we use CSCs to establish non-adherent sphere cultures, 3D tumor organoids, and xenografts. Treatment with WNT and NOTCH inhibitors blocks the proliferation and self-renewal of CSCs in sphere cultures and organoids, and impairs tumor growth in patient-derived xenografts in mice. These findings suggest that our approach is a promising route towards the development of personalized treatments for individual patients

Salen-Based Amphiphiles:Directing Self-Assembly in Water by Metal Complexation

Tuning morphologies of self‐assembled structures in water is a major challenge. Herein we present a salen‐based amphiphile which, using complexation with distinct transition metal ions, allows to control effectively the self‐assembly morphology in water, as observed by Cryo‐TEM and confirmed by DLS measurements. Applying this strategy with various metal ions gives a broad spectrum of self‐assembled structures starting from the same amphiphilic ligand (from cubic structures to vesicles and micelles). Thermogravimetric analysis and electric conductivity measurements reveal a key role for water coordination apparently being responsible for the distinct assembly behavior.Supramolecular & Biomaterials Chemistr