Optimisation and molecular signalling of apoptosis in sequential cryotherapy and chemotherapy combination in human A549 lung cancer xenografts in SCID mice

We define the optimal parameters for combination of cryotherapy (nitrous oxide) with chemotherapy (vinorelbine ditartrate, VNB) treatment and characterise some of the signals involved for apoptosis activation. No advantage appeared when cryotherapy and VNB were combined simultaneously compared to cryosurgery alone. In contrast, tumour volumes were reduced after a sequential treatment schedule, where each individual treatment was separated by 48 h. No significant benefit appeared when the sequential treatment was separated by 24 h, although some individual mice showed a good response. The sequence of treatment had no impact on the observed tumour growth inhibition in mice. The number of apoptotic cells was significantly augmented in the sequential treatment schedule where VNB was administered 48 h before cryotherapy. In this sequential treatment, the number of apoptotic cells correlated with heightened expression of the BH3-only Puma, Noxa and Bim-EL, at both the mRNA and protein levels. No significant change in Bax, Bcl-xL and Bcl-2 mRNA expression was apparent, whereas Mcl-1 expression increased only slightly to a much lower level than BH3-only mRNAs. Our data indicate that 48 h sequential rather than simultaneous cryotherapy with VNB in future cancer cryochemotherapy schedules will enhance the tumour response, and argue that VNB administration, 48 h before cryotherapy, will provoke apoptosis more efficiently

Biomedical informatics and translational medicine

Biomedical informatics involves a core set of methodologies that can provide a foundation for crossing the "translational barriers" associated with translational medicine. To this end, the fundamental aspects of biomedical informatics (e.g., bioinformatics, imaging informatics, clinical informatics, and public health informatics) may be essential in helping improve the ability to bring basic research findings to the bedside, evaluate the efficacy of interventions across communities, and enable the assessment of the eventual impact of translational medicine innovations on health policies. Here, a brief description is provided for a selection of key biomedical informatics topics (Decision Support, Natural Language Processing, Standards, Information Retrieval, and Electronic Health Records) and their relevance to translational medicine. Based on contributions and advancements in each of these topic areas, the article proposes that biomedical informatics practitioners ("biomedical informaticians") can be essential members of translational medicine teams