Activity of cabazitaxel in castration-resistant prostate cancer progressing after docetaxel and next-generation endocrine agents

Background Cabazitaxel, abiraterone, and enzalutamide are survival-prolonging treatments in men with castration-resistant prostate cancer (CRPC) progressing following docetaxel chemotherapy. The sequential activity of these agents has not been studied and treatment sequencing remains a key dilemma for clinicians. Objective To describe the antitumour activity of cabazitaxel after docetaxel and next-generation endocrine agents. Design, setting, and participants We report on a cohort of 59 men with progressing CRPC treated with cabazitaxel, 37 of whom had received prior abiraterone and 9 of whom had received prior enzalutamide. Outcome measurements and statistical analysis Changes in prostate-specific antigen (PSA) level were used to determine activity on abiraterone, enzalutamide, and cabazitaxel treatment. Radiologic tumour regressions according to Response Evaluation Criteria in Solid Tumors (RECIST) and symptomatic benefit were evaluated for cabazitaxel therapy. Results and limitations The post-endocrine-therapy patients received abiraterone (n = 32), sequential abiraterone and enzalutamide (n = 5) or enzalutamide (n = 4). These patients received a median of 7 mo of abiraterone and 11 mo of enzalutamide. A median of six cabazitaxel cycles (range: 1-10 cycles) were delivered, with ≥50% PSA declines in 16 of 41 (39%) patients, soft tissue radiologic responses in 3 of 22 (14%) evaluable patients, and symptomatic benefit in 9 of 37 evaluable patients (24%). Median overall survival and progression-free survival were 15.8 and 4.6 mo, respectively. Antitumor activity on cabazitaxel was less favourable in the abiraterone- and enzalutamide-naïve cohort (n = 18), likely reflecting biologic differences in this cohort. These data were obtained from a retrospective analysis. Conclusions This is the first report of cabazitaxel activity in CRPC progressing after treatment with docetaxel and abiraterone or enzalutamide. We demonstrate significant cabazitaxel activity in this setting. Patient summary We looked at the antitumour activity of the chemotherapy drug cabazitaxel in men previously treated with docetaxel chemotherapy and the hormonal drugs abiraterone and enzalutamide. Cabazitaxel appeared active when given after abiraterone and enzalutamide. We can reassure men that cabazitaxel can be used after these novel endocrine treatments. © 2013 European Association of Urology.

A proposed approach to systematically identify and monitor the corporate political activity of the food industry with respect to public health using publicly available information.

Unhealthy diets represent one of the major risk factors for non-communicable diseases. There is currently a risk that the political influence of the food industry results in public health policies that do not adequately balance public and commercial interests. This paper aims to develop a framework for categorizing the corporate political activity of the food industry with respect to public health and proposes an approach to systematically identify and monitor it. The proposed framework includes six strategies used by the food industry to influence public health policies and outcomes: information and messaging; financial incentive; constituency building; legal; policy substitution; opposition fragmentation and destabilization. The corporate political activity of the food industry could be identified and monitored through publicly available data sourced from the industry itself, governments, the media and other sources. Steps for country-level monitoring include identification of key food industry actors and related sources of information, followed by systematic data collection and analysis of relevant documents, using the proposed framework as a basis for classification of results. The proposed monitoring approach should be pilot tested in different countries as part of efforts to increase the transparency and accountability of the food industry. This approach has the potential to help redress any imbalance of interests and thereby contribute to the prevention and control of non-communicable diseases.

Reduction of the photocatalytic activity of ZnO by impurity doping

 The thesis systematically presents several methods to synthesize the photocatalytic activity reduced ZnO by impurity doping and coating which is suitable for many commercial and medical applications in sun-screening area. The author has published one book chapter and many high quality journal papers.

Role of muscarinic receptors in the activity of N-desmethylclozapine: reversal of hyperactivity in the phospholipase C knockout mouse

Activity of the cholinergic muscarinic system is associated with modulation of locomotor activity, although the precise mechanism remains unclear. The phospholipase C-[beta]1 knockout mouse displays both M1 muscarinic receptor dysfunction and a hyperactive locomotor phenotype. This mouse serves as an ideal model for the analysis of muscarinic modulation of locomotor activity. The clozapine metabolite N-desmethylclozapine (NDMC) has shown some promise as an alternative or adjunct treatment for psychotic disorders. NDMC shows strong muscarinic acetylcholine receptor affinities, which may contribute to the clinical efficacy of clozapine and account for the correlation between NDMC/clozapine ratio and treatment response. Administration of NMDC reversed a striking hyperactive phenotype in the phospholipase C-[beta]1 knockout mouse, whereas no significant effects were observed in wild-type animals. This highlights the potential role of muscarinic activity in the behavioural response to NDMC. The M1 muscarinic antagonist pirenzepine, however, also reduced the hyperactive phenotype of these mice, emphasizing the importance of muscarinic function in the control of locomotor behaviour, but also calling into question the specific mechanism of action of NMDC at muscarinic receptors.

Antimanic-like activity of candesartan in mice: possible involvement of antioxidant, anti-inflammatory and neurotrophic mechanisms

Activation of the brain angiotensin II type 1 receptor (AT1R) triggers pro-oxidant and pro-inflammatory mechanisms which are involved in the neurobiology of bipolar disorder (BD). Candesartan (CDS) is an AT1 receptor antagonist with potential neuroprotective properties. Herein we investigated CDS effects against oxidative, neurotrophic inflammatory and cognitive effects of amphetamine (AMPH)-induced mania. In the reversal protocol adult mice were given AMPH 2mg/kg i.p. or saline and between days 8 and 14 received CDS 0.1, 0.3 or 1mg/kg orally, lithium (Li) 47.5mg/kg i.p., or saline. In the prevention treatment, mice were pretreated with CDS, Li or saline prior to AMPH. Locomotor activity and working memory performance were assessed. Glutathione (GSH), thiobarbituric acid-reactive substance (TBARS) and TNF-α levels were evaluated in the hippocampus (HC) and cerebellar vermis (CV). Brain-derived neurotrophic factor (BDNF) and glycogen synthase kinase 3-beta (GSK-3beta) levels were measured in the HC. CDS and Li prevented and reversed the AMPH-induced increases in locomotor activity. Only CDS prevented and reversed AMPH-induced working memory deficits. CDS prevented AMPH-induced alterations in GSH (HC and CV), TBARS (HC and CV), TNF-α (HC and CV) and BDNF (HC) levels. Li prevented alterations in BDNF and phospho-Ser9-GSK3beta. CDS reversed AMPH-induced alterations in GSH (HC and CV), TBARS (HC), TNF-α (CV) and BDNF levels. Li reversed AMPH-induced alterations in TNF-α (HC and CV) and BDNF (HC) levels. CDS is effective in reversing and preventing AMPH-induced behavioral and biochemical alterations, providing a rationale for the design of clinical trials investigating CDS׳s possible therapeutic effects.

Systematic examination of publicly-available information reveals the diverse and extensive corporate political activity of the food industry in Australia

BACKGROUND: The political influence of the food industry, referred to as corporate political activity (CPA), represents a potential barrier to the development and implementation of effective public health policies for non-communicable diseases prevention. This paper reports on the feasibility and limitations of using publicly-available information to identify and monitor the CPA of the food industry in Australia. METHODS: A systematic search was conducted for information from food industry, government and other publicly-available data sources in Australia. Data was collected in relation to five key food industry actors: the Australian Food and Grocery Council; Coca Cola; McDonald's; Nestle; and Woolworths, for the period January 2012 to February 2015. Data analysis was guided by an existing framework for classifying CPA strategies of the food industry. RESULTS: The selected food industry actors used multiple CPA strategies, with 'information and messaging' and 'constituency building' strategies most prominent. CONCLUSIONS: The systematic analysis of publicly-available information over a limited period was able to identify diverse and extensive CPA strategies of the food industry in Australia. This approach can contribute to accountability mechanisms for NCD prevention.