A qualitative evaluation of community and acute hospital nursing oncology services in Ireland.

Purpose: Cancer patients are a particularly vulnerable population group, facing an increase in physical, mental, logistical and financial difficulties. This, as well as Ireland's increased focus on primary care with the Sláintecare health plan, led to the development of the Community Oncology Nursing Programme, where community nurses are trained to provide cancer care in the community. This paper sought to explore the lived experiences of the patients and nurses involved in this programme in order to examine its impact as well as determine facilitators and roadblocks for future development.

A cost comparison study to review community versus acute hospital models of nursing care delivered to oncology patients.

Purpose: Ireland's Sláintecare health plan is placing an increased focus on primary care. A community oncology nursing programme was developed to train community nurses to deliver care in the community. While the initial pilot was proven to be clinically safe, no cost evaluation was carried out.

Safety, Tolerability and Pharmacokinetics of FAAH Inhibitor V158866: A Double-Blind, Randomised, Placebo-Controlled Phase I Study in Healthy Volunteers.

Background And Objective: The inhibition of fatty acid amide hydrolase 1 (FAAH) has been proposed as a novel mechanism for treating pain syndromes by increasing the levels of endogenous cannabinoids (ECs). This study describes the safety, tolerability, pharmacokinetics and pharmacodynamics of V158866, a reversible FAAH inhibitor, after first administration to man.

Methods: 51 healthy male subjects were recruited into this double-blind, randomised, placebo-controlled, adaptive dose, phase I single (Part A) and repeated ascending dose (Part B) study.

Identification of novel, in vivo active Chk1 inhibitors utilizing structure guided drug design.

Chk1 kinase is a critical component of the DNA damage response checkpoint especially in cancer cells and targeting Chk1 is a potential therapeutic opportunity for potentiating the anti-tumor activity of DNA damaging chemotherapy drugs. Fragment elaboration by structure guided design was utilized to identify and develop a novel series of Chk1 inhibitors culminating in the identification of V158411, a potent ATP-competitive inhibitor of the Chk1 and Chk2 kinases. V158411 abrogated gemcitabine and camptothecin induced cell cycle checkpoints, resulting in the expected modulation of cell cycle proteins and increased cell death in cancer cells.

Targeting conserved water molecules: design of 4-aryl-5-cyanopyrrolo[2,3-d]pyrimidine Hsp90 inhibitors using fragment-based screening and structure-based optimization.

Inhibitors of the Hsp90 molecular chaperone are showing promise as anti-cancer agents. Here we describe a series of 4-aryl-5-cyanopyrrolo[2,3-d]pyrimidine ATP competitive Hsp90 inhibitors that were identified following structure-driven optimization of purine hits revealed by NMR based screening of a proprietary fragment library. Ligand-Hsp90 X-ray structures combined with molecular modeling led to the rational displacement of a conserved water molecule leading to enhanced affinity for Hsp90 as measured by fluorescence polarization, isothermal titration calorimetry and surface plasmon resonance assays.

Fatty acid amide hydrolase inhibitors. 3: tetra-substituted azetidine ureas with in vivo activity.

We describe here our attempts to optimise the human fatty acid amide hydrolase (FAAH) inhibition and physicochemical properties of our previously reported tetrasubstituted azetidine urea FAAH inhibitor, VER-156084. We describe the SAR of a series of analogues and conclude with the demonstration of in vivo dose-dependant FAAH inhibition in an anandamide-loading study in rats.

A novel, small molecule inhibitor of Hsc70/Hsp70 potentiates Hsp90 inhibitor induced apoptosis in HCT116 colon carcinoma cells.

Purpose: The anti-apoptotic function of the 70 kDa family of heat shock proteins and their role in cancer is well documented. Dual targeting of Hsc70 and Hsp70 with siRNA induces proteasome-dependent degradation of Hsp90 client proteins and extensive tumor specific apoptosis as well as the potentiation of tumor cell apoptosis following pharmacological Hsp90 inhibition.

Methods: We have previously described the discovery and synthesis of novel adenosine-derived inhibitors of the 70 kDa family of heat shock proteins; the first inhibitors described to target the ATPase binding domain.

The determinants of therapeutic levels of continuous positive airway pressure in elderly sleep apnea patients.

We have examined the role of age on the continuous positive airway pressure (CPAP) levels required to treat two groups of elderly (n=70) and young (n=70) sleep apneic patients, matched for disease severity (apnea/hypopnea index), body mass index and neck circumference. Elderly patients required lower CPAP levels compared to young [mean (sd): 6.9(1.

Antitumor benzothiazoles. Frontier molecular orbital analysis predicts bioactivation of 2-(4-aminophenyl)benzothiazoles to reactive intermediates by cytochrome P4501A1.

The antitumor and metabolic activities of 2-(4-aminophenyl)benzothiazoles and their fluorinated analogues cannot be explained or predicted by conventional chemical means. Their mode of anti-cancer action involves metabolism of the benzothiazoles to an as yet unidentified reactive species. This species then forms DNA adducts which provoke cell death.