A Century of Fractionated Radiotherapy: How Mathematical Oncology Can Break the Rules.

Radiotherapy is involved in 50% of all cancer treatments and 40% of cancer cures. Most of these treatments are delivered in fractions of equal doses of radiation (Fractional Equivalent Dosing (FED)) in days to weeks. This treatment paradigm has remained unchanged in the past century and does not account for the development of radioresistance during treatment. Even if under-optimized, deviating from a century of successful therapy delivered in FED can be difficult. One way of exploring the infinite space of fraction size and scheduling to identify optimal fractionation schedules is through mathematical oncology simulations that allow for in silico evaluation. This review article explores the evidence that current fractionation promotes the development of radioresistance, summarizes mathematical solutions to account for radioresistance, both in the curative and non-curative setting, and reviews current clinical data investigating non-FED fractionated radiotherapy.

Exposure to Moderate Glycosuria Induces Virulence of Group B Streptococcus.

To explore whether glycosuria induces virulence of uropathogens, in turn facilitating urinary tract infection (UTI), we exposed group B Streptococcus (GBS) strain 10/84 to human urine plain or with 300 mg/dL glucose (mimicking moderate glycosuria). Exposure to moderate glycosuria significantly augmented bacterial growth, kidney bacterial burden in a mouse model of ascending UTI, and virulence characteristics and expression of corresponding genes. Exposure to glycosuria increased GBS adherence to human bladder epithelial cell line and expression of corresponding PI2a fimbrial gene, antimicrobial peptide LL-37 resistance and bacterial surface charge modulating dltA, and GBS hemolytic ability and expression of genes encoding pore-forming toxins.