BackgroundOsteosarcoma is an orphan disease for which little improvement in survival has been made since the late 1980s. New drug discovery for orphan diseases is limited by the cost and time it takes to develop new drugs. Repurposing already approved FDA-drugs can help overcome this limitation. Another limitation of cancer drug discovery is the lack of preclinical models that accurately recapitulate what occurs in humans. For OS using dogs as a model can minimize this limitation as OS in canines develops spontaneously, is locally invasive and metastasizes to the lungs as it does in humans.MethodsIn our present work we used high-throughput screens to identify drugs from a library of 2,286 FDA-approved drugs that demonstrated selective growth inhibition against both human and canine OS cell lines. The identified lead compound was then tested for synergy with 7 other drugs that have demonstrated activity against OS. These results were confirmed with in vitro assays and an in vivo murine model of OS.ResultsWe identified 13 drugs that demonstrated selective growth inhibition against both human and canine OS cell lines. Auranofin was selected for further in vitro combination drug screens. Auranofin showed synergistic effects with vorinostat and rapamycin on OS viability and apoptosis induction. Auranofin demonstrated single-agent growth inhibition in both human and canine OS xenografts, and cooperative growth inhibition was observed in combination with rapamycin or vorinostat. There was a significant decrease in Ki67-positive cells and an increase in cleaved caspase-3 levels in tumor tissues treated with a combination of auranofin and vorinostat or rapamycin.ConclusionsAuranofin, alone or in combination with rapamycin or vorinostat, may be useful new treatment strategies for OS. Future studies may evaluate the efficacy of auranofin in dogs with OS as a prelude to human clinical evaluation.

Nasal colonization of methicillin-resistant Staphylococcus aureus (MRSA) plays an important role in the epidemiology and pathogenesis of disease. Situations of close-quarter contact in groups are generally regarded as a risk factor for community-acquired MRSA strains due to transmission via fomites and person-to-person contact. With these criteria for risk, homeless individuals using shelter facilities, including showers and toilets, should be considered high risk for colonization and infection. The aim of this study was to determine the prevalence of nasal colonization of MRSA in a homeless population compared to established rates of colonization within the public and a control group of subjects from a neighboring medical school campus, and to analyze phylogenetic diversity among the MRSA strains. Nasal samples were taken from the study population of 332 adult participants and analyzed. In addition, participants were surveyed about various lifestyle factors in order to elucidate potential patterns of behavior associated with MRSA colonization. Homeless and control groups both had higher prevalence of MRSA (9.8 and 10.6%, respectively), when compared to the general population reported by previous studies (1.8%). However, the control group had a similar MRSA rate compared to health-care workers (4.6%), while the homeless population had an increased prevalence. Risk factors identified in this study included male gender, age over 50 years, and use of antibiotics within the past 3 months. Phylogenetic relationships between nine of the positive samples from the homeless population were analyzed, showing eight of the nine samples had a high degree of relatedness between the spaA genes of the MRSA strains. This indicates that the same MRSA strain might be transmitted from person-to-person among homeless population. These findings increase our understanding of key differences in MRSA characteristics within homeless populations, as well as risks for MRSA associated with being homeless, such as age and gender, which may then be a useful tool in guiding more effective prevention, treatment, and health care for homeless individuals.

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Background Congenital pulmonary airway malformations (CPAMs) are a heterogenous collection of congenital lung malformations, often diagnosed prenatally. The Stocker Type III CPAM is a rare CPAM sub-type, and, when large, may be associated with hydrops. Furthermore, reports of CPAM management which may include surgical resection in extreme preterm infants are limited. Case presentation We report a case of a female neonate born at 28 weeks of gestation with severe respiratory distress and diffuse pulmonary opacification on the right concerning for a large congenital lung lesion. This lesion was not detected on routine antenatal imaging, and she did not have clinical findings of associated hydrops. Her respiratory status improved dramatically after surgical resection of a mass at 12 day of age. The mass was consistent pathologically with a Stocker Type III CPAM. Lung expansion showed subsequent improvement at 16 months of age. Conclusions Our case describes a preterm neonate with severe respiratory distress that was found postnatally to have a large, unilateral congenital lung lesion despite a normal prenatal ultrasound. Additionally, this lesion required excision early in life due to severity of respiratory compromise. This case highlights that rare congenital lung lesions, like this rare sub-type of CPAM, should remain a diagnostic consideration in neonates with severe respiratory distress. Early lung resection for CPAM in preterm infants is not well described and the favorable outcomes of this case help expand perspectives on potential management strategies.