Clinically Approved Carbon Nanoparticles with Oral Administration for Intestinal Radioprotection via Protecting the Small Intestinal Crypt Stem Cells and Maintaining the Balance of Intestinal Flora

Small ◽  
2020 ◽  
Vol 16 (16) ◽  
pp. 1906915 ◽  
Author(s):  
Chengyan Wang ◽  
Jiani Xie ◽  
Xinghua Dong ◽  
Linqiang Mei ◽  
Maoru Zhao ◽  
...  
2014 ◽  
Vol 55 (2) ◽  
pp. 381-390 ◽  
Author(s):  
Motohiro Yamauchi ◽  
Kensuke Otsuka ◽  
Hisayoshi Kondo ◽  
Nobuyuki Hamada ◽  
Masanori Tomita ◽  
...  

2012 ◽  
Vol 303 (11) ◽  
pp. G1188-G1201 ◽  
Author(s):  
Kevin R. Hughes ◽  
Ricardo M. C. Gândara ◽  
Tanvi Javkar ◽  
Fred Sablitzky ◽  
Hanno Hock ◽  
...  

Stem cells have been identified in two locations in small intestinal crypts; those intercalated between Paneth cells and another population (which retains DNA label) are located above the Paneth cell zone, at cell position 4. Because of disadvantages associated with the use of DNA label, doxycycline-induced transient transgenic expression of histone 2B (H2B)-green fluorescent protein (GFP) was investigated. H2B-GFP-retaining putative stem cells were consistently seen, with a peak at cell position 4, over chase periods of up to 112 days. After a 28-day chase, a subpopulation of the H2B-GFP-retaining cells was cycling, but the slow cycling status of the majority was illustrated by lack of expression of pHistone H3 and Ki67. Although some H2B-GFP-retaining cells were sensitive to low-dose radiation, the majority was resistant to low- and high-dose radiation-induced cell death, and a proportion of the surviving cells proliferated during subsequent epithelial regeneration. Long-term retention of H2B-GFP in a subpopulation of small intestinal Paneth cells was also seen, implying that they are long lived. In contrast to the small intestine, H2B-GFP-retaining epithelial cells were not seen in the colon from 28-day chase onward. This implies important differences in stem cell function between these two regions of the gastrointestinal tract, which may have implications for region-specific susceptibility to diseases (such as cancer and ulcerative colitis), in which epithelial stem cells and their progeny are involved.


2017 ◽  
Vol 31 (S1) ◽  
Author(s):  
Kunihiro Kishida ◽  
Sarah Pearce ◽  
Shiyan Yu ◽  
Nan Gao ◽  
Ronaldo Ferraris

2019 ◽  
Author(s):  
Michael M Lübtow ◽  
Sabrina Oertner ◽  
Sabina Quader ◽  
Elisabeth Jeanclos ◽  
Alevtina Cubukova ◽  
...  

Inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase of the family of statins have been suggested as therapeutic options in various tumors. Atorvastatin is a statin with potential to cross the blood-brain-barrier, however, the concentrations necessary for a cytotoxic effect against cancer cells exceeds the concentration achievable via oral administration, which made the development of a novel atorvastatin formulation necessary. We characterized the drug loading and basic physicochemical characteristics of micellar atorvastatin formulations and tested their cytotoxicity against a panel of different glioblastoma cell lines. In addition, activity against tumor spheroids formed from mouse glioma and mouse cancer stem cells, respectively, was evaluated. Our results show good activity of atorvastatin against all tested cell lines. Interestingly, in the 3D models, growth inhibition was more pronounced for the micellar formulation compared to free atorvastatin. Finally, atorvastatin penetration across a blood-brain-barrier model obtained from human induced-pluripotent stem cells was evaluated. Our results suggest that the presented micelles may enable much higher serum concentrations than possible by oral administration, however, if transport across the blood-brain-barrier is sufficient to reach therapeutic atorvastatin concentration for the treatment of glioblastoma via intravenous administration remains unclear.<br>


1998 ◽  
Vol 241 (2) ◽  
pp. 316-323 ◽  
Author(s):  
K. Martin ◽  
T.B.L. Kirkwood ◽  
C.S. Potten

1958 ◽  
Vol 2 (3) ◽  
pp. 225-230 ◽  
Author(s):  
Shogo Kuwahara ◽  
Hiroshi Nakahara ◽  
Seiichiro Yasushi ◽  
Kikuno Ota ◽  
Mie Takano

Biomaterials ◽  
2011 ◽  
Vol 32 (5) ◽  
pp. 1317-1326 ◽  
Author(s):  
Shaofeng Wu ◽  
Yan Liu ◽  
Shantaram Bharadwaj ◽  
Anthony Atala ◽  
Yuanyuan Zhang

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