Carcinogenesis involves uncontrolled cell growth, which follows the activation of oncogenes and/or the deactivation of tumor suppression genes. Metastasis requires down-regulation of cell adhesion receptors necessary for tissue-specific, cell–cell attachment, as well as up-regulation of receptors that enhance cell motility. Epigenetic changes, including histone modifications, DNA methylation, and DNA hydroxymethylation, can modify these characteristics. Targets for these epigenetic changes include signaling pathways that regulate apoptosis and autophagy, as well as microRNA. We propose that predisposed normal cells convert to cancer progenitor cells that, after growing, undergo an epithelial-mesenchymal transition. This process, which is partially under epigenetic control, can create a metastatic form of both progenitor and full-fledged cancer cells, after which metastasis to a distant location may occur. Identification of epigenetic regulatory mechanisms has provided potential therapeutic avenues. In particular, epigenetic drugs appear to potentiate the action of traditional therapeutics, often by demethylating and re-expressing tumor suppressor genes to inhibit tumorigenesis. Epigenetic drugs may inhibit both the formation and growth of cancer progenitor cells, thus reducing the recurrence of cancer. Adopting epigenetic alteration as a new hallmark of cancer is a logical and necessary step that will further encourage the development of novel epigenetic biomarkers and therapeutics.

The modern patient is increasingly susceptible to bacterial infections including those due to multi-drug resistant organisms (MDROs). Noninvasive whole-body analysis with pathogen-specific imaging technologies can significantly improve patient outcomes by rapidly identifying a source of infection and monitoring the response to treatment, but no such technology exists clinically. Methods We systematically screened 961 random, radiolabeled molecules in silico as substrates for essential metabolic pathways in bacteria, followed by in vitro uptake in representative bacteria – Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and mycobacteria. Fluorine-labeled analogs, that could be developed as positron emission tomography (PET)-based imaging tracers, were evaluated in a murine myositis model. Results We identified three novel, non-toxic molecules demonstrating selective bacterial uptake: para-aminobenzoic acid (PABA), with uptake in all representative bacteria including Mycobacterium tuberculosis; mannitol, with selectively uptake in S. aureus and E. coli; and sorbitol, accumulating only in E. coli. None accumulated in mammalian cells or heat-killed bacteria, suggesting metabolism-derived specificity. In addition to an extended bacterial panel of laboratory strains, all three molecules rapidly accumulated in respective clinical isolates of interest including MDROs such as methicillin resistant S. aureus (MRSA), extended-spectrum beta-lactamase (ESBL)-producing, and carbapenem-resistant Enterobacteriaceae. In a murine myositis model, fluorine-labeled analogs of all three molecules could rapidly detect and differentiate infection sites from sterile inflammation in mice (P=0.03). Finally, 2-deoxy-2-[F-18]fluoro-D-sorbitol (18F-FDS) can be easily synthesized from 2-deoxy-2-[F-18]fluoro-D-glucose (18F-FDG). PET, utilizing 18F-FDS synthesized using current good manufacturing practice, could rapidly differentiate true infection from sterile inflammation to selectively localize E. coli infection in mice. Conclusion We have developed a systematic approach that exploits unique biochemical pathways in bacteria to develop novel pathogen-specific imaging tracers. These tracers have significant potential for clinical translation to specifically detect and localize a broad range of bacteria, including MDROs.

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Congenital lobar emphysema (CLE) and congenital pulmonary lymphangiectasis (CPL) are rare conditions that are most often identified with prenatal ultrasonography. Occasionally, this disease process is first identified in the emergency department (ED), where the physician should avoid common pitfalls in order to prevent acute decompensation. To the best of our knowledge, there are no prior reports in the emergency medicine literature of CLE or CPL presenting to the ED as undifferentiated respiratory distress in an infant. Here, we describe one such case and then discuss the importance of differentiating these congenital anomalies from more commonly encountered emergency diagnoses, such as pneumothorax and pneumonia. Management differs radically, and the use of chest tubes and positive pressure ventilation in CLE may precipitate acute cardiovascular decompensation.