p-toluene sulfonamide (p-TSA), a small molecular drug with antineoplastic activity is widely gaining interest from researchers because of its pharmacological activities. In this study, we explored the potential cardio and neural toxicity of p-TSA in sublethal concentrations by using zebrafish as an in vivo animal model. Based on the acute toxicity assay, the 96hr LC50 was estimated as 204.3 ppm, suggesting the overall toxicity of p-TSA is relatively low in zebrafish larvae. For the cardiotoxicity test, we found that p-TSA caused only a minor alteration in treated larvae after no overall significant alterations were observed in cardiac rhythm and cardiac physiology parameters, as supported by the results from expression level measurements of several cardiac development marker genes. On the other hand, we found that acute p-TSA exposure significantly increased the larval locomotion activity during the photomotor test while prolonged exposure (4 days) reduced the locomotor startle reflex activities in zebrafish. In addition, a higher respiratory rate and blood flow velocity was also observed in the acutely treated fish groups compared to the untreated group. Finally, by molecular docking, we found that p-TSA has a moderate binding affinity to skeletal muscle myosin II subfragment 1 (S1), ATPase activity, actin- and Ca2+-stimulated myosin S1 ATPase, and v-type proton ATPase. These binding interactions between p-TSA and proteins offer insights into the potential molecular mechanism of action of p-TSA on observed altered responses toward photo and vibration stimuli and minor altered vascular performance in the zebrafish larvae.

Combine modality anti-cancer treatment, Concurrent Chemo-Radio Therapy (CCRT) is a recommended approach for relatively resistant tumor in clinical oncology. But it is relatively more toxic to patient, and severely disrupt patient’s quality of life due to systemic side-effects causing by intravenous cytotoxic drugs delivery, especially for those fragile advanced cancer patients. Intra-arterial infusion chemotherapy is another option for CCRT because of not only a better tumor respond documented, and also bonus a better quality of life improvement. We demonstrated an advanced buccal cancer patient who had been heavily treated, but rapidly recurrence head and neck tumor for salvage treatment with Intra-Arterial Concurrent Chemo-Radio Therapy (IACCRT). Complete tumor respond was resulted, and also restored a very satisfactory gain on quality of life, ECOG had been improved from score 3 to 1. We concluded that IACCRT is a feasible treatment choice for fragile advanced cancer patient.