Xionggui Jiaoai Decoction

Multidrug resistance and toxic side effects are the major challenges in cancer treatment with microtubule-targeting agents (MTAs), and thus, there is an urgent clinical need for new therapies. Chalcone, a common simple scaffold found in many natural products, is widely used as a privileged structure in medicinal chemistry. We have previously validated tubulin as the anticancer target for chalcone derivatives. In this study, an α-methyl-substituted indole-chalcone (FC77) was synthesized and found to exhibit an excellent cytotoxicity against the NCI-60 cell lines (average concentration causing 50% growth inhibition = 6 nM). More importantly, several multidrug-resistant cancer cell lines showed no resistance to FC77, and the compound demonstrated good selective toxicity against cancer cells versus normal CD34⁺ blood progenitor cells. A further mechanistic study demonstrated that FC77 could arrest cells that relate to the binding to tubulin and inhibit the microtubule dynamics. The National Cancer Institute COMPARE analysis and molecular modeling indicated that FC77 had a mechanism of action similar to that of colchicine. Overall, our data demonstrate that this indole-chalcone represents a novel MTA template for further development of potential drug candidates for the treatment of multidrug-resistant cancers.

Pediatric patients are susceptible to lung injury that does not respond to traditional therapies. Partial liquid ventilation (PLV) has been developed as an alternative ventilatory strategy for treating severe lung injury. The aim of this study is to investigate the effect of PLV on lung function in immature piglets.

Acute lung injury was induced in 12 Chinese immature piglets by oleic acid (OA). The animals were randomly assigned to two groups (n=6 each group): (1) conventional mechanical ventilation (MV) group and (2) PLV with FC-77 (10 ml/kg) group. Mean arterial blood pressure (MAP), mean pulmonary arterial pressure (MPAP), central venous pressure (CVP), left atrial pressure (LAP), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), cardiac output (CO), mean pressure of airway (Paw), dynamic lung compliance (Cydn), and arterial blood gases were measured during the observation period.

No piglet died in either group with severe lung injury. After four hours of ventilation, pH in the MV group gradually decreased to lower than 7.20, while in the PLV group, pH also gradually decreased but remained higher than 7.20 (P <0.05). Partial pressure of oxygen in artery (PaO2) decreased in both groups, but with a significant difference between the PLV group and MV group (P <0.05). Partial pressure of carbon dioxide in artery (PaCO2) increased in both groups, but with a significant difference between the PLV group and MV group (P <0.05). Paw increased in both groups, but was not significantly different (P >0.05). Cydn decreased in both groups, but without a significant difference (P >0.05). At four hours, heart rate (HR) and MAP in both groups decreased. MPAP in both groups increased, and there was a significant difference between the two groups (P <0.05). CVP was stable in both groups. At four hours, PVR and LAP were increased in both groups. CO was decreased in both groups (P <0.05). SVR was stable during the observation time.

PLV did not improve outcome in changes of lung function.