[Radium-223 for the treatment of metastatic castration-resistant prostate cancer (mCRPC) : The androgen receptor-independent active agent in the therapeutic sequence]. / Radium-223 zur Therapie des metastasierten kastrationsresistenten Prostatakarzinoms (mCRPC) : Der androgenrezeptorunabhängige Wirkstoff in der therapeutischen Sequenz.

BACKGROUND: Radium-223 improves overall survival and preserves quality of life in patients with metastatic castration-resistant prostate cancer (mCRPC) and symptomatic bone metastases and no known visceral metastases. Radium-223 can be used in combination with a luteinizing hormone releasing hormone (LHRH) analogue and as part of a sequential treatment scheme if disease progresses after at least two prior lines of systemic mCRPC therapies or if no other available systemic treatment is eligible. OBJECTIVES: Today physicians are faced with a previously unknown multitude and complexity of options for the treatment of mCRPC. An increasing number of clinical trials contribute to the dynamics of the therapeutic landscape. Radium-223 was approved for mCRPC treatment in 2013. Up to now the recommendations of use have been adjusted several times. Highlighting recent clinical trials and practice, this paper explores the position of radium-223 within the therapeutic sequence and outlines key elements for the interdisciplinary cooperation between uro-oncologists and nuclear medicine specialists. RESULTS: The mode of action of radium-223 does not depend on the androgen receptor (AR) pathway. Thus, it is an option in the therapeutic sequence when the efficacy of other agents is reduced by resistance. Furthermore, the efficacy of prior or subsequent medications are neither reduced nor enhanced by radium-223. The opportunity of an AR-independent and survival-prolonging medication should be taken as soon as the indication criteria are met because the incidence of visceral metastases increases during disease progression. According to current mCRPC guidelines, the osteoprotective use of bisphosphonates or denosumab is recommended, before treatment with radium-223 is started or resumed.

[Metastatic castration-resistant prostate cancer : Use of cabazitaxel taking into consideration current data]. / Metastasiertes kastrationsresistentes Prostatakarzinom : Neues zu Cabazitaxel unter Berücksichtigung der aktuellen Datenlage.

BACKGROUND: At the 2016 ASCO annual meeting, new data from two randomized phase III studies concerning taxane-based chemotherapy as a treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC) were presented. OBJECTIVES: The focus is on the clinical impact of these data. MATERIALS AND METHODS: A group of German experts in the field of urogenital-oncologic expertise discussed the clinical impact with respect to the current data. RESULTS: The study results support the current clinical data. They confirm the efficacy and safety of cabazitaxel beyond first-line therapy with docetaxel for patients with mCRPC. CONCLUSIONS: Cabazitaxel is an important treatment option after docetaxel progression. With respect to the performance status of a patient, it is adequate to reduce the dosage to 20 mg/m2 cabazitaxel.

[Metastatic prostate cancer : Update: position paper for the use of chemotherapy]. / Metastasiertes Prostatakarzinom : Update: Positionspapier zum Einsatz der Chemotherapie.

BACKGROUND: Taxen-based chemotherapy has been established as an effective treatment option in castration-resistant metastatic prostate cancer (mCRPC). Randomized phase III studies, however, have shown that even in the hormone-naïve metastatic state, the early use of chemotherapy in addition to the classical androgen deprivation therapy (ADT) approach leads to a significant increase in median overall survival. OBJECTIVE: This position paper aims to provide current data and orientation in the evidence-based treatment of mPC patients in daily clinical practice. MATERIALS AND METHODS: A German group of clinical experts analyzed the current data and developed criteria for the treatment of mPC patients in daily clinical practice. RESULTS: In the current treatment of hormone-naïve mPC, a beneficial effect of chemotherapy in addition to ADT has become evident. Provided patients are in an appropriate condition, those with a high metastatic load should receive chemotherapy in addition to ADT. Especially in high-risk mCRPC patients (PSA >114 ng/ml, visceral metastasis, ADT response <12 months, tumor-associated complaints), first-line chemotherapy is indicated. After docetaxel failure, continuous treatment with cabazitaxel shows superior overall survival compared to sustained antihormonal therapy. CONCLUSION: Chemotherapy is firmly established in treating patients with mCRPC. Long-term, it will be important to identify molecular predictors. The authors suggest the early use of chemotherapy in hormone-naïve mPC, but note that the approval in this indication is currently nonexistent. After disease progression, patients should be treated analogous to mCRPC.

Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015.

REASONS FOR PERFORMING STUDY: New therapeutic strategies to modulate immune responses in human and equine allergic airway diseases are under extensive investigation. Stimulation of Treg cells with immune modulating agents is a novel therapeutic option. OBJECTIVES: The aim of this field study was to compare the effects of a nebulised nanoparticulate CpG immunotherapy (CpG-GNP) with and without specific allergens. STUDY DESIGN: Longitudinal clinical study comparing 2 therapeutic options. METHODS: Twenty RAO-affected horses were divided into 2 treatment groups (CpG alone and CpG with allergens). Two specific allergens were selected for each horse according to anamnesis and a functional in vitro test. Treatments were given by nebulisation 7 times and the horses were examined 3 times: baseline (I), after the treatment course (II), and after 6 weeks later (III). Clinical parameters, indirect intrapleural measurement, arterial blood gas, amount of tracheal mucus and neutrophil percentage were evaluated. RESULTS: CpG alone resulted in a significant improvement in clinical parameters and a significant reduction of tracheal mucus after treatment and at 6 weeks post treatment. After CpG plus specific allergens, there was significant improvement of 70% of examined parameters. However, there were no significant differences in the results compared with CpG-GNP treatment alone. CONCLUSIONS: There were no significant differences between treatment groups. CpG-GNP immunotherapy alone produced a potent and persistent effect on allergic and inflammatory parameters and may have potential as for treatment of equine and human allergic inflammatory airway diseases. Ethical animal research: The study was approved by the regional legal agency for animal experiments of the Government of Bavaria, Germany (No. 55.2-1-54-2531-31-10). Owners gave informed consent for their horses' inclusion in the study. Sources of funding: Partly supported by the Deutsche Forschungsgemeinschaft (DFG) (Germany) (GE'2044/4-1). The AeroNeb Go™ vibrating mesh nebuliser (Aerogen, Galway, Ireland) was sponsored by Inspiration Medical (Bochum, Germany). Competing interests: None declared.

Nanoparticulate CpG immunotherapy in RAO-affected horses: phase I and IIa study.

BACKGROUND: Recurrent airway obstruction (RAO), an asthma-like disease, is 1 of the most common allergic diseases in horses in the northern hemisphere. Hypersensitivity reactions to environmental antigens cause an allergic inflammatory response in the equine airways. Cytosine-phosphate-guanosine-oligodeoxynucleotides (CpG-ODN) are known to direct the immune system toward a Th1-pathway, and away from the pro-allergic Th2-line (Th2/Th1-shift). Gelatin nanoparticles (GNPs) are biocompatible and biodegradable immunological inert drug delivery systems that protect CpG-ODN against nuclease degeneration. Preliminary studies on the inhalation of GNP-bound CpG-ODN in RAO-affected horses have shown promising results. OBJECTIVES: The aim of this study was to evaluate the clinical and immunological effects of GNP-bound CpG-ODN in a double-blinded, placebo-controlled, prospective, randomized clinical trial and to verify a sustained effect post-treatment. ANIMALS AND METHODS: Twenty-four RAO-affected horses received 1 inhalation every 2 days for 5 consecutive administrations. Horses were examined for clinical, endoscopic, cytological, and blood biochemical variables before the inhalation regimen (I), immediately afterwards (II), and 4 weeks post-treatment (III). RESULTS: At time points I and II, administration of treatment rather than placebo corresponded to a statistically significant decrease in respiratory effort, nasal discharge, tracheal secretion, and viscosity, AaDO2 and neutrophil percentage, and an increase in arterial oxygen pressure. CONCLUSION AND CLINICAL IMPORTANCE: Administration of a GNP-bound CpG-ODN formulation caused a potent and persistent effect on allergic and inflammatory-induced clinical variables in RAO-affected horses. This treatment, therefore, provides an innovative, promising, and well-tolerated strategy beyond conventional symptomatic long-term therapy and could serve as a model for asthma treatment in humans.

Triple-point wetting on rough substrates.

The influence of substrate roughness on the wetting scenario of adsorbed van der Waals films is investigated by theory and experiment. Calculating the bending free energy penalty of a solid sheet picking up the substrate roughness, we show that a finite roughness always leads to triple-point wetting reducing the widths of the adsorbed solid films considerably as compared to that of smooth substrates. Testing the theory against our experimental data for molecular hydrogen adsorbed on gold, we find quantitative agreement.

Model for the extreme wetting hysteresis of liquid helium on cesium

Although the liquid- 4He-cesium system is a nearly ideal one for studying wetting phenomena, it can show extreme hysteresis which is profoundly nonideal in behavior. It is suggested that this is due to the roughness of these Cs surfaces. We show that stable micropuddles of liquid 4He can form in shallow cavities on a Cs surface. It is the potential to form micropuddles, as the liquid tries to recede, which pins the contact line due to the large energy needed to create the surface of a micropuddle. This model also accounts for the memory that these surfaces have of being in contact with liquid 4He.

Equilibrium swelling of poly(methacrylic acid-g-ethylene glycol) hydrogels. Effect of swelling medium and synthesis conditions.

Responsive hydrogel networks comprising of poly(methacrylic acid) (PMAA) backbone and oligomeric ethylene glycol (PEG) grafts were synthesized by free-radical solution polymerization and their equilibrium swelling properties were characterized in aqueous solutions of a homologous series of alcohols. These hydrogels are known to exhibit swelling transitions in response to external stimuli which lead to formation or disruption of hydrogen-bonded complexes between the backbone and the grafts. Swelling studies performed in aqueous mixtures of methanol, ethanol and propanol revealed that the effectiveness of an alcohol in breaking the PMAA/PEG complexes increased as the aliphatic segment length of the alcohol was increased. These results confirm the importance of hydrophobic interactions for stabilizing the complexes. Studies performed to determine the effect of the synthesis conditions on the equilibrium swelling properties revealed that the equilibrium degree of swelling increased as the solvent fraction during synthesis was increased. Finally, molecular stimulations revealed that it is sterically possible to form complexes with a 1:1 stoichiometry between chains of poly(methacrylic acid) and poly(ethylene glycol) with essentially no additional bond strain.

Oxygen limitation on L-serine production in a hollow-fiber bioreactor.

Pseudomonas AM1 utilizes glycine and methanol to produce L-serine aerobically. The consumption of methanol in this bioconversion is stoichiometrically in excess of L-serine production. Consequently, the oxygen requirement associated with L-serine production is higher than expected for the conversion from glycine. One method of L-serine production investigated was a technique utilizing a hollow-fiber ultrafiltration cartridge as a bioreactor. Oxygen diffusion limitations appear to impede the consumption of methanol and, consequently, the production of L-serine in such a reactor. Methanol consumption data agree with predictions based on a hollow-fiber diffusion model.

Beyond permanency planning.

With permanency planning taking the spotlight increasingly in the field of foster care, it becomes urgent to examine the definition of permanency, the effect on practice, and the implications for service delivery.