Oxfendazole

Emerging studies have reported the potential anticancer activity of benzimidazole-based anthelmintics (BBA) against lung cancer (LC). However, mechanism underlying the anticancer activity of BBA is unclear. Therefore, in the current study, network pharmacology and molecular docking-based approach were used to explore the potential molecular mechanism for the treatment of LC. The potential targets for BBA were obtained from multiple databases including SwissTargetPrediction, Drug Bank, Therapeutic Target Database, and Comparative Toxicogenomics Database while LC targets were collected from DisGeNet gene discovery platform, Integrated Genomic Database of NSCLC, Catalogue of Somatic Mutations in Cancer and Online Mendelian Inheritance in Man database. Protein-protein interaction (PPI) diagram of common targets was constructed using STRING online platform. Topological analysis was performed using Cytoscape and gene enrichment analysis was conducted using FunRich software. Highest degree targets were then confirmed using molecular docking and molecular dynamics simulations. The BBA were prioritized according to their S scores, with ricobendazole ranking highest followed by flubendazole, fenbendazole, mebendazole, triclabendazole, albendazole, oxibendazole, parbendazole, thiabendazole and oxfendazole. The potential targets of BBA identified using topological analysis and molecular docking were found to be CCND1 (cyclin D1), EGFR (Epidermal Growth Factor Receptor), ERBB2 (Erb-B2 Receptor Tyrosine Kinase 2/CD340), PTGS2 (Prostaglandin-endoperoxide synthase 2), and SRC (Proto-oncogene tyrosine-protein kinase). Furthermore, molecular dynamics confirmed that CCND1 and EGFR are the potential targets of ricobendazole for the treatment of LC. BBA can be further explored as a therapeutic strategy for the treatment of lung cancer under in vitro and in vivo studies.Communicated by Ramaswamy H. Sarma.

Strongyloides stercoralis is a worldwide occurring nematode infecting canids and primates (including humans), responsible for a largely underestimated zoonotic disease. We here present 18 cases including overall 20 dogs affected by S. stercoralis, diagnosed in Switzerland between 2010 and 2020. The Baermann examination was positive for S. stercoralis larvae in 10, suspicious in 4, negative in one and not performed in 2 dogs. In 3 dogs the infection was identified only at necropsy by histology or by direct faecal or mucosal smears from intestinal tissue. Confirmation of suspected, necropsied and Baermann-negative dogs relied on genetic analyses. Twelve dogs had a history of import from Eastern Europe (n=4), the Mediterranean basin (n=5) or Germany (n=3). They were 7 weeks to 9,5 months old, and also the dogs supposedly born in Switzerland were younger than one year (except two, aged 15 months and 14 years). Thirteen dogs were males and 6 females (1 unknown). The most represented breeds were Chihuahuas (n=5), French Bulldogs (n=4) and Pomeranians (n=3). The most frequent clinical sign and reason for presentation was diarrhoea, occurring in 11/20 animals. Further gastrointestinal symptoms were vomiting, anorexia/hyporexia, adipsia, dehydration, tense abdomen and tenesmus. Respiratory symptoms were the second most frequent, with coughing in 7/20 animals, followed by tachypnoea/dyspnoea in 5 and (reverse) sneezing in 3 dogs. Treatment with 50 mg/kg BW fenbendazole p.o. over 5 days was successful in 4 cases in which a follow-up examination was performed 3-6 weeks later; prolonged treatment over 21 days was also effective. Ivermectin off-label protocols described in the literature, e.g. 0,8 mg/kg BW s.c. or 0,5 mg/kg BW i.m. repeated after 2 weeks, were successful based on control examinations performed 3-10 weeks later. Strongyloides stercoralis infections are clinically relevant, potentially zoonotic and need to be included in differential diagnoses in case of canine gastrointestinal and respiratory disorders, especially in young and imported dogs.