Enhancing anti-cancer capacity: Novel class I/II HDAC inhibitors modulate EMT, cell cycle, and apoptosis pathways.

Cancer has been a leading cause of death over the last few decades in western countries as well as in Taiwan. However, traditional therapies are limited by the adverse effects of chemotherapy and radiotherapy, and tumor recurrence may occur. Therefore, it is critical to develop novel therapeutic drugs. In the field of HDAC inhibitor development, apart from the hydroxamic acid moiety, 2-aminobenzamide also functions as a zinc-binding domain, which is shown in well-known HDAC inhibitors such as Entinostat and Chidamide. With recent successful experiences in synthesizing 1-(phenylsulfonyl)indole-based compounds, in this study, we further combined two features of the above chemical compounds and generated indolyl benzamides. Compounds were screened in different cancer cell lines, and enzyme activity was examined to demonstrate their potential for anti-HDAC activity. Various biological functional assays evidenced that two of these compounds could suppress cancer growth and migration capacity, through regulating epithelial-mesenchymal transition (EMT), cell cycle, and apoptosis mechanisms. Data from 3D cancer cells and the in vivo zebrafish model suggested the potential of these compounds in cancer therapy in the future.

Botulinum toxin for lower limb spasticity in children with cerebral palsy: a single-blinded trial comparing dilution techniques.

OBJECTIVE: To compare the effect of equivalent doses of botulinum toxin type A given in high-volume or low-volume injections on lower limb spasticity in children with cerebral palsy. DESIGN: A total of 17 subjects whose modified Ashworth scale scores in the calf flexors bilaterally ranged from 2 to 3 were enrolled. The right gastrocnemius was injected with botulinum toxin type A using a high-volume preparation (100 IU/4 ml), and the left gastrocnemius was injected with a low-volume preparation (100 IU/1 ml). The amplitude and area of the compound muscle action potential for both medial gastrocnemius muscles, the dynamic muscle range, static muscle range, modified Ashworth scale for both ankles, and the Gross Motor Functional Classification System were assessed before and after treatment. RESULTS: Spasticity was reduced in both legs. There was no significant difference in the changes in the amplitude and area of compound muscle action potential (P = 0.74 and 0.30, respectively), dynamic muscle range (P = 0.7), static muscle range (P = 0.65), and modified Ashworth scale (P = 1) in the right vs. left legs after botulinum toxin type A injection. The high-volume preparation did not cause more pain. CONCLUSIONS: A higher volume preparation with a 4-fold dilution of botulinum toxin type A does not yield better results than a low-volume preparation.