Soluble amyloid
β protein (A
β)1–40 and highly amyloidogenic A
β1–42/43 were immunocytochemically labeled in lysosomes of acinar cells and macrophages in the pancreas of transgenic mice systemically ...expressing a C-terminal fragment of the A
β precursor. A
β1–42/43 and long A
β species extending their C-termini were detected in the detergent-insoluble fraction. Immunoreactivity of cathepsin D was markedly increased in lysosomes filled with A
β fibrils. These findings indicated that A
β1–40, A
β1–42, A
β1–43 and longer A
β species were generated in the lysosomes of the transgenic pancreas, and suggested that the activation of cathepsin D, a candidate
γ-secretase, leads to acceleration of A
β amyloid formation.
Targeted alpha therapy is receiving much attention in the field of theranostics because of its high cytotoxic effect to the targeting cancer cells. However, physiological uptakes in non-targeted ...organs are also observed in the targeted alpha therapy, which might lead to the severe side effects. We should consider about both maximizing the treatment effect in the tumor and minimizing the side effects in the organs at risk. From this viewpoint, decision of targeting molecule was most important.We selected LAT1 as molecular target. LAT1 is one of the amino acid transporters. LAT1 has highly specificity to cancer tissues. We developed next-generation internal radiotherapy using chemicals targeting LAT1. First, we synthesized alpha-methyl-L-tylosine labeled with 211At. 211At was produced by the cyclotron, and then quickly purified and combined to alpha-methyl-L-tyrosine (211At-AAMT). Next, we performed cytotoxicity evaluation of 211At-AAMT using PANC-1 cells, Human pancreas cancer cell lines. We also detected the DNA damage by 211At-AAMT. As a result, cell death and specificity were confirmed in 211At-AAMT. We also found the anti-cancer effects in vivo study. In the immediate future, we will examine that the effects of 211At-AAMT using several kinds of tumor-bearing models.
We can define the space of railway stations as a combination of the main building, space of style, and the train shed, space of function. We aim to clarify what kind of space the structual ...development of train shed wanted to realize and found out the fact that the development of train shed was due to conservartory engineer's ideas of big space originated from cathedral and after that some of railway and conservatory engineers adopted its techniques and systems of construction. Finally, we examined the historical transition of the relationship between main building and train shed and its backgrounds and located train shed's position in architectural history.
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