Combining repurposed drugs to treat colorectal cancer.

The drug development process, especially of antineoplastic agents, has become increasingly costly and ineffective. Drug repurposing and drug combination are alternatives to de novo drug development, being low cost, rapid, and easy to apply. These strategies allow higher efficacy, decreased toxicity, and overcoming of drug resistance. The combination of antineoplastic agents is already being applied in cancer therapy, but the combination of repurposed drugs is still under-explored in pre- and clinical development. In this review, we provide a set of pharmacological concepts focusing on drug repurposing for treating colorectal cancer (CRC) and that are relevant for the application of new drug combinations against this disease.

Cryptosporidium and Giardia in tropical recreational marine waters contaminated with domestic sewage: estimation of bathing-associated disease risks.

Sewage is a major contributor to pollution problems involving human pathogens in tropical coastal areas. This study investigated the occurrence of intestinal protozoan parasites (Giardia and Cryptosporidium) in tropical recreational marine waters contaminated with sewage. The potential risks of Cryptosporidium and Giardia infection from recreational water exposure were estimated from the levels of viable (oo) cysts (DIC+, DAPI+, PI-) found in near-shore swimming areas using an exponential dose response model. A Monte Carlo uncertainty analysis was performed in order to determine the probability distribution of risks. Microbial indicators of recreational water quality (enterococci, Clostridium perfringens) and genetic markers of sewage pollution (human-specific Bacteroidales marker [HF183] and Clostridium coccoides) were simultaneously evaluated in order to estimate the extent of water quality deterioration associated with human wastes. The study revealed the potential risk of parasite infections via primary contact with tropical marine waters contaminated with sewage; higher risk estimates for Giardia than for Cryptosporidium were found. Mean risks estimated by Monte Carlo were below the U.S. EPA upper bound on recreational risk of 0.036 for cryptosporidiosis and giardiasis for both children and adults. However, 95th percentile estimates for giardiasis for children exceeded the 0.036 level. Environmental surveillance of microbial pathogens is crucial in order to control and eradicate the effects that increasing anthropogenic impacts have on marine ecosystems and human health.