Powerpoint versus Traditional Overheads. Which Is More Effective for Learning

Abstract

L-arginine/nitric oxide pathway metabolites are altered in colorectal cancer (CRC). We evaluated underlying changes in pathway enzymes in 55 paired tumor/tumor-adjacent samples and 20 normal mucosa using quantitative-PCR and assessed the impact of classic and novel oxicam analogues on enzyme expression and intracellular metabolite concentration (LC-MS/MS) in Caco-2, HCT116, and HT-29 cells. Compared to normal mucosa, <i>ARG1</i>, <i>PRMT1,</i> and <i>PRMT5</i> were overexpressed in both tumor and tumor-adjacent tissue and <i>DDAH2</i> solely in tumor-adjacent tissue. Tumor-adjacent tissue had higher expression of <i>ARG1</i>, <i>DDAH1</i>, and <i>DDAH2</i> and lower <i>NOS2</i> than patients-matched tumors. The <i>ARG1</i> expression in tumors increased along with tumor grade and reflected lymph node involvement. Novel oxicam analogues with arylpiperazine moiety at the thiazine ring were more effective in downregulating <i>DDAHs</i> and <i>PRMTs</i> and upregulating <i>ARG2</i> than piroxicam and meloxicam. An analogue distinguished by propylene linker between thiazine's and piperazine's nitrogen atoms and containing two fluorine substituents was the strongest inhibitor of <i>DDAHs</i> and <i>PRMTs</i> expression, while an analogue containing propylene linker but no fluorine substituents was the strongest inhibitor of <i>ARG2</i> expression. Metabolic reprogramming in CRC includes overexpression of <i>DDAHs</i> and <i>PRMTs</i> in addition to <i>ARG1</i> and <i>NOS2</i> and is not restricted to tumor tissue but can be modulated by novel oxicam analogues.