In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain

2006 ◽  
Vol 56 (5) ◽  
pp. 1001-1010 ◽  
Author(s):  
Chris Heyn ◽  
John A. Ronald ◽  
Soha S. Ramadan ◽  
Jonatan A. Snir ◽  
Andrea M. Barry ◽  
...  
2011 ◽  
Vol 46 (11) ◽  
pp. 718-725 ◽  
Author(s):  
Dean B. Percy ◽  
Emeline J. Ribot ◽  
Yuhua Chen ◽  
Catherine McFadden ◽  
Carmen Simedrea ◽  
...  

2021 ◽  
Author(s):  
Othman Benchama ◽  
Sergiy Tyukhtenko ◽  
Michael S. Malamas ◽  
Mark K. Williams ◽  
Alexandros Makriyannis ◽  
...  

Abstract While the prevalence of breast cancer metastasis in the brain is significantly higher in triple negative breast cancers (TNBCs), there is a lack of novel and/or improved therapies for these patients. Monoacylglycerol lipase (MAGL) is a hydrolase involved in lipid metabolism that catalyzes the degradation of 2-arachidonoylglycerol (2-AG) linked to generation of pro- and anti-inflammatory molecules. Here, we targeted MAGL in TNBCs, using the selective MAGL inhibitor AM9928 (hMAGL IC50 = 9nM, with prolonged pharmacodynamic effects of 46 hours residence time). AM9928 blocked TNBC cell adhesion and transmigration across human brain microvascular endothelial cells (HBMECs) in 3D co-cultures. In addition, AM9928 inhibited the secretion of IL-6, IL-8, and VEGF-A from TNBC cells. TNBC-derived exosomes activated HBMECs resulting in secretion of elevated levels of IL-8 and VEGF, which were inhibited by AM9928. Knockdown of MAGL by siRNA or treatment with AM9928 increased the expression of the adherent junction E-cadherin, known to be regulated by MAGL. Using in vivo studies of syngeneic GFP-4T1-BrM5 mammary tumor cells, AM9928 inhibited tumor growth in the mammary fat pads and attenuated blood brain barrier (BBB) permeability changes, resulting in reduced TNBC colonization in brain. Together, these results support the potential clinical application of MAGL inhibitors as novel treatments for TNBC.


2016 ◽  
Author(s):  
Minna Ampuja ◽  
Emma L. Alarmo ◽  
Philip Owens ◽  
Riikka Havunen ◽  
Agnes E. Gorska ◽  
...  

2020 ◽  
Vol 21 (21) ◽  
pp. 7896
Author(s):  
Jun Nakayama ◽  
Ryohei Saito ◽  
Yusuke Hayashi ◽  
Nobuo Kitada ◽  
Shota Tamaki ◽  
...  

Bioluminescence imaging (BLI) is useful to monitor cell movement and gene expression in live animals. However, D-luciferin has a short wavelength (560 nm) which is absorbed by tissues and the use of near-infrared (NIR) luciferin analogues enable high sensitivity in vivo BLI. The AkaLumine-AkaLuc BLI system (Aka-BLI) can detect resolution at the single-cell level; however, it has a clear hepatic background signal. Here, to enable the highly sensitive detection of bioluminescence from the surrounding liver tissues, we focused on seMpai (C15H16N3O2S) which has been synthesized as a luciferin analogue and has high luminescent abilities as same as AkaLumine. We demonstrated that seMpai BLI could detect micro-signals near the liver without any background signal. The solution of seMpai was neutral; therefore, seMpai imaging did not cause any adverse effect in mice. seMpai enabled a highly sensitive in vivo BLI as compared to previous techniques. Our findings suggest that the development of a novel mutated luciferase against seMpai may enable a highly sensitive BLI at the single-cell level without any background signal. Novel seMpai BLI system can be used for in vivo imaging in the fields of life sciences and medicine.


2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii4-iii4
Author(s):  
Mao Li ◽  
Markus Schweiger ◽  
Ichiro Nakano ◽  
Daniel Ryan ◽  
Litia Carvalho ◽  
...  

Abstract Olfactory receptors (ORs), responsible for the sense of smell, play an essential role in physiological processes (even outside the nasal epithelium) and cancer. In breast cancer, however, the expression and role of ORs remain understudied. We examined the significance of ORs transcript abundance in breast cancer metastasis to different tissues including the brain, bone, and lung. While we found 20 OR genes to be differentially expressed in different metastasis versus primary tumor, OR5B21 displayed high relation with all metastases. Knockdown of OR5B21 significantly decreased the invasion and migration of breast cancer cells in culture as well as metastasis to different organs including the brain, in vivo. On the other hand, overexpression of OR5B21 in the primary cells had the opposite effect. Mechanistically, OR5B21 was associated with epithelial to mesenchymal transition through STAT3/NFkB/CEBPβ signaling pathway. We propose OR5B21 (and potentially other ORs) as a novel oncogene contributing to breast cancer metastasis, and as a potential target for therapy.


2021 ◽  
Vol 22 (11) ◽  
pp. 5988
Author(s):  
Hyun Kyu Kim ◽  
Tae Won Ha ◽  
Man Ryul Lee

Cells are the basic units of all organisms and are involved in all vital activities, such as proliferation, differentiation, senescence, and apoptosis. A human body consists of more than 30 trillion cells generated through repeated division and differentiation from a single-cell fertilized egg in a highly organized programmatic fashion. Since the recent formation of the Human Cell Atlas consortium, establishing the Human Cell Atlas at the single-cell level has been an ongoing activity with the goal of understanding the mechanisms underlying diseases and vital cellular activities at the level of the single cell. In particular, transcriptome analysis of embryonic stem cells at the single-cell level is of great importance, as these cells are responsible for determining cell fate. Here, we review single-cell analysis techniques that have been actively used in recent years, introduce the single-cell analysis studies currently in progress in pluripotent stem cells and reprogramming, and forecast future studies.


2008 ◽  
Vol 27 (2) ◽  
pp. 97-105 ◽  
Author(s):  
Cimona V. Hinton ◽  
Shalom Avraham ◽  
Hava Karsenty Avraham

2020 ◽  
Author(s):  
Juliane Winkler ◽  
Weilun Tan ◽  
Christopher McGinnis ◽  
Zev Gartner ◽  
Spyros Darmanis ◽  
...  

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