Insulin-Like Growth Factor-1 Receptor Targeted Fluorescent Imaging for Gallbladder Cancer in Orthotopic Mouse Models

Background/Aims@#Gallbladder cancer is fatal, but fluorescent imaging technology can facilitate timely diagnosis and improve patient outcomes. Fluorophore-conjugated insulin-like growth factor-1 receptor (IGF-1R) targeted antibodies were used to visualize gallbladder cancer in orthotopic tumor mouse models. @*Methods@#Western blotting, flow cytometric analysis, and confocal microscopy detected the expression of IGF-1R in SNU-308, SNU-478, and SNU-1196 bile duct cancer cells. In vivo imaging of SNU-478 and SNU-1196 subcutaneous tumors and orthotopic gallbladder tumor models of SNU-478 were performed after injection with DyLight 650-conjugated IGF-1R antibody. @*Results@#Western blotting and flow cytometric analysis showed that IGF-1R was expressed in bile duct cancer cells, and confocal microscopy demonstrated that IGF-1R antibody was able to bind to IGF-1R on the cell membrane. Fluorescent IGF-1R antibody injected into the mouse tail vein made subcutaneous tumors and orthotopic tumors become fluorescent. The intensity of fluorescence from the tumor was stronger than that from surrounding normal tissues. Histochemical examination confirmed that the tumor was located inside the gallbladder and adjacent liver parenchyma of mice. @*Conclusions@#Our study showed that a fluorescent IGF-1R-targeted antibody could help detect gallbladder tumors. Tumor-specific imaging technology can be applied to endoscopy, laparoscopy, and robotic surgery for better management of gallbladder cancer.

Intracellular amyloid beta interacts with SOD1 and impairs the enzymatic activity of SOD1: implications for the pathogenesis of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the degeneration of motor neurons. Mutations in Cu/Zn superoxide dismutase (SOD1), including G93A, were reportedly linked to familial ALS. SOD1 is a key antioxidant enzyme, and is also one of the major targets for oxidative damage in the brains of patients suffering from Alzheimer's disease (AD). Several lines of evidence suggest that intracellular amyloid beta (Abeta) is associated with the pathogenesis of AD. In this report we demonstrate that intracellular Abeta directly interacts with SOD1, and that this interaction decreases the enzymatic activity of the enzyme. We observed Abeta-SOD1 aggregates in the perinuclear region of H4 cells, and mapped the SOD1 binding region to Abeta amino acids 26-42. Interestingly, intracellular Abeta binds to the SOD1 G93A mutant with greater affinity than to wild-type SOD1. This resulted in considerably less mutant enzymatic activity. Our study implicates a potential role for Abeta in the development of ALS by interacting with the SOD1 G93A mutant.