Intensifying Salvage Therapy in Prostate-specific Antigen Recurrent Prostate Cancer After Radical Prostatectomy with Apalutamide, Salvage Radiation, and Docetaxel: The Phase 2 STARTAR Trial.

Background And Objective: Androgen deprivation therapy (ADT) with salvage radiation therapy (RT) improves survival for patients with prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP) for prostate cancer (PC), but many patients suffer further relapse. This study aims to determine the benefit of the combination of ADT, apalutamide, salvage RT, and docetaxel for high-risk PSA recurrent PC.

Methods: STARTAR is a multicenter, investigator-initiated phase 2 trial of men with PSA recurrent PC after RP.

Unexpected Stability of a Prodrug to Enzymatic Hydrolysis within a Hydrated HPMC Matrix Tablet.

The uptake of alkaline phosphate present in dissolution medium into a hydrating hydroxypropyl methylcellulose matrix tablet and that its activity was retained therein was demonstrated. This presents a risk to the stability of prodrugs that are substrates of this enzyme such as phosphonooxymethyl derivative prodrugs. It was found that fostemsavir, a phosphonooxymethyl derivative prodrug being developed for the treatment of HIV-1 infection, was unexpectedly resistant to hydrolysis within a hydrated HPMC matrix when subjected to drug release testing in media containing alkaline phosphatase.

Having permission not to remember: perspectives on interventions for post-traumatic stress disorder in the absence of trauma memory.

Background: It is possible for people to have post-traumatic stress disorder (PTSD) without memory of the trauma event, such as in drug-facilitated sexual assault. However, there is little evidence available on treatment provision for this population.

Objective: This study aimed to address this gap by exploring the experiences of people who have had psychological intervention for PTSD without memories (PwM).

A phase 2 trial of avelumab in men with aggressive-variant or neuroendocrine prostate cancer.

Background: Men with progressive neuroendocrine or aggressive-variant metastatic prostate cancer (NEPC/AVPC) have a poor prognosis and limited treatment options, and immunotherapy has not been tested in such patients.

Methods: We conducted an open label single center phase 2 trial (NCT03179410) of men with progressive NEPC/AVPC either defined by histology or AVPC criteria. Avelumab (10 mg/kg every 2 weeks) was administered until progression or unacceptable toxicity.

Pharmacodynamic study of radium-223 in men with bone metastatic castration resistant prostate cancer.

Background: Radium-223 is a targeted alpha-particle therapy that improves survival in men with metastatic castration resistant prostate cancer (mCRPC), particularly in men with elevated serum levels of bone alkaline phosphatase (B-ALP). We hypothesized that osteomimicry, a form of epithelial plasticity leading to an osteoblastic phenotype, may contribute to intralesional deposition of radium-223 and subsequent irradiation of the tumor microenvironment.

Methods: We conducted a pharmacodynamic study (NCT02204943) of radium-223 in men with bone mCRPC.

Determination of 2-Hydroxypyridine-1-Oxide (HOPO) at sub-ppm levels using derivitization and gas chromatography with mass spectrometry detection (GCMS).

This work describes the development and validation of an analytical method to determine residual trace levels of 2-Hydroxypyridine-1-Oxide (HOPO) in an active pharmaceutical ingredient (API). A method was required to be specific and sensitive enough to determine sub-ppm levels of this reagent. The approach taken to use a derivitization step overcame two of the primary challenges associated with the analysis of HOPO.

Cigarette smoke-induced Ca2+ release leads to cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction.

Chronic obstructive pulmonary disease affects 64 million people and is currently the fourth leading cause of death worldwide. Chronic obstructive pulmonary disease includes both emphysema and chronic bronchitis, and in the case of chronic bronchitis represents an inflammatory response of the airways that is associated with mucus hypersecretion and obstruction of small airways. Recently, it has emerged that exposure to cigarette smoke (CS) leads to an inhibition of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel, causing airway surface liquid dehydration, which may play a role in the development of chronic bronchitis.

Nonantibiotic macrolides prevent human neutrophil elastase-induced mucus stasis and airway surface liquid volume depletion.

Mucus clearance is an important component of the lung's innate defense system. A failure of this system brought on by mucus dehydration is common to both cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). Mucus clearance rates are regulated by the volume of airway surface liquid (ASL) and by ciliary beat frequency (CBF).

Cigarette smoke exposure induces CFTR internalization and insolubility, leading to airway surface liquid dehydration.

Cigarette smoke (CS) exposure induces mucus obstruction and the development of chronic bronchitis (CB). While many of these responses are determined genetically, little is known about the effects CS can exert on pulmonary epithelia at the protein level. We, therefore, tested the hypothesis that CS exerts direct effects on the CFTR protein, which could impair airway hydration, leading to the mucus stasis characteristic of both cystic fibrosis and CB.

TGFbeta3 and loading increases osteocyte survival in human cancellous bone cultured ex vivo.

The goal of this study was to assess the effect of the addition of TGFbeta(3), alone or in combination with loading, on the survival of osteocytes in 3D human explant cancellous bone during long-term culture in an ex vivo loading bioreactor. Human cancellous bone explants were cultured for up to 14 days with or without TGFbeta(3) (15 ng ml(-1)) and with or without loading (300 cycles, at 1 Hz, producing 4000 microstrain). Bone core response was visualized using undecalcified histology with morphological methods after embedding with Technovit 9100 New resin.

Oxidative DNA damage in osteoarthritic porcine articular cartilage.

Osteoarthritis (OA) is associated with increased levels of reactive oxygen species. This study investigated if increased oxidative DNA damage accumulates in OA articular cartilage compared with non-OA articular cartilage from pigs with spontaneous OA. Additionally, the ability of nitric oxide (NO) or peroxynitrite (ONOO(-)) induced DNA damage in non-OA chondrocytes to undergo endogenous repair was investigated.