Multi-wavelength Optical Imaging of Human Tumour Xenografts

2011 ◽  
Vol 64 (5) ◽  
pp. 625 ◽  
Author(s):  
Wei Wang ◽  
Arlin G. Cameron ◽  
Juliet A. Wendt ◽  
Michel E. Mawad ◽  
Shi Ke

In vivo optical imaging methods have become a cornerstone of pre-clinical cancer research. Genetically modified cells with fluorescent or bioluminescent reporters allow researchers to non-invasively study tumour proliferation and biochemistry over time. Target-specific fluorescent probes may be used to reveal specific tumour properties such as growth patterns, neovasculature formation, and compartmental probe absorbance. Herein, we demonstrate the simultaneous optical imaging of these tumour properties in a human neuroblastoma model. We used luciferase-positive cancer cells, a neovasculature specific fluorescent probe, and a fluorescent tumour cell target-specific agent, in conjunction with X-ray/CT for anatomical localization. These experiments revealed a detailed map of the tumour progression and biological interactions with imaging agents within the tumour.

2017 ◽  
Author(s):  
Christopher A. Dacosta ◽  
Claudia Paicu ◽  
Irina Mohorianu ◽  
Wei Wang ◽  
Ping Xu ◽  
...  

AbstractColorectal cancer is an increasingly important cause of morbidity and mortality, whose incidence is associated with dietary and lifestyle factors, particularly inversely so with the consumption of cruciferous vegetables. These vegetables contain glucosinolates, from the breakdown of which are derived isothiocyanates, such as sulforaphane. Sulforaphane is well-characterised for wide-ranging tumour-suppressive and chemoprotective activities in vitro, yet deeper elucidation of its biological interactions would aid in better realising its potential in chemoprevention and/or chemotherapy. There is evidence to suggest that sulforaphane modulates microRNA expression in the colon, thus implying the potential for microRNA modulation to play a role in the anti-cancer effects of sulforaphane. Therefore, the effects of sulforaphane on microRNA expression profiles in the colonic adenocarcinoma Caco-2 and non-cancerous colonic CCD-841 cell lines were investigated by small RNA cloning and deep sequencing, followed by Northern Blot validation experiments. Sulforaphane upregulated let-7f-5p and let-7g-5p expression at 24 h in Caco-2 cells, but not in CCD-841. Such treatment also downregulated miR-29b-3p in Caco-2. Dual luciferase assays with a let-7f-5p mimic and inhibitor confirmed the binding of the miRNA to predicted binding sites in the mRNA transcript 3’-UTRs of cell division cycle 25A (CDC25A), high-mobility group AT-hook-2 (HMGA2) and MYC. Therefore, we hypothesize that let-7f-5p translationally represses CDC25A, HMGA2 and MYC, thereby playing a role in the tumour-suppressive effects of sulforaphane. The apparent selectivity of let-7f-5p induction towards tumour cells would be therapeutically desirable if applicable in vivo. MiR-29b-3p is predicted to target a number of tumour-suppressing genes, further investigation of which could be informative regarding the potential of sulforaphane to suppress tumour progression.


2016 ◽  
Vol 55 (02) ◽  
pp. 51-62 ◽  
Author(s):  
S. Hermann ◽  
M. Schäfers ◽  
C. Höltke ◽  
A. Faust

SummaryOptical imaging has long been considered a method for histological or microscopic investigations. Over the last 15 years, however, this method was applied for preclinical molecular imaging and, just recently, was also able to show its principal potential for clinical applications (e.g. fluorescence-guided surgery). Reviewing the development and preclinical evaluation of new fluorescent dyes and target-specific dye conjugates, these often show characteristic patterns of their routes of excretion and biodistribution, which could also be interesting for the development and optimization of radiopharmaceuticals. Especially ionic charges show a great influence on biodistribution and netcharge and charge-distribution on a conjugate often determines unspecific binding or background signals in liver, kidney or intestine, and other organs.Learning from fluorescent probe behaviour in vivo and translating this knowledge to radio-pharmaceuticals might be useful to further optimize emerging and existing radiopharmaceuticals with respect to their biodistribution and thereby availability for binding to their targets.


2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Guangyu Ji ◽  
Wenjuan Zhou ◽  
Jingyi Du ◽  
Juan Zhou ◽  
Dong Wu ◽  
...  

AbstractColorectal cancer (CRC) stem cells are resistant to cancer therapy and are therefore responsible for tumour progression after conventional therapy fails. However, the molecular mechanisms underlying the maintenance of stemness are poorly understood. In this study, we identified PCGF1 as a crucial epigenetic regulator that sustains the stem cell-like phenotype of CRC. PCGF1 expression was increased in CRC and was significantly correlated with cancer progression and poor prognosis in CRC patients. PCGF1 knockdown inhibited CRC stem cell proliferation and CRC stem cell enrichment. Importantly, PCGF1 silencing impaired tumour growth in vivo. Mechanistically, PCGF1 bound to the promoters of CRC stem cell markers and activated their transcription by increasing the H3K4 histone trimethylation (H3K4me3) marks and decreasing the H3K27 histone trimethylation (H3K27me3) marks on their promoters by increasing expression of the H3K4me3 methyltransferase KMT2A and the H3K27me3 demethylase KDM6A. Our findings suggest that PCGF1 is a potential therapeutic target for CRC treatment.


2014 ◽  
Vol 10 (1) ◽  
pp. 187-195 ◽  
Author(s):  
Yoichi Shimizu ◽  
Takashi Temma ◽  
Isao Hara ◽  
Akira Makino ◽  
Ryo Yamahara ◽  
...  

Theranostics ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. 45-60 ◽  
Author(s):  
Jah Yeon Choi ◽  
Jiheun Ryu ◽  
Hyun Jung Kim ◽  
Joon Woo Song ◽  
Joo Hee Jeon ◽  
...  

Endocrinology ◽  
2012 ◽  
Vol 153 (6) ◽  
pp. 2907-2918 ◽  
Author(s):  
Katrin Büther ◽  
Matthijs G. Compeer ◽  
Jo G. R. De Mey ◽  
Otmar Schober ◽  
Michael Schäfers ◽  
...  

Endothelin (ET) receptor dysregulation has been described in a number of pathophysiological processes, including cardiovascular disorders, renal failure, and cancer. The aim of this study was to evaluate the expression of the ET-A receptor (ETAR) in murine models of thyroid carcinoma using optical imaging methods. A recently developed near-infrared fluorescent tracer was first assessed in isolated artery preparations for its functional performance in comparison with known ETAR antagonists BQ123 and PD156707. Before evaluation of the tracer in vivo, different thyroid carcinoma cell lines were characterized with respect to their ET receptor expression by RT-PCR and autoradiography. In vivo, sc and orthotopic papillary thyroid tumor xenografts were clearly visualized by fluorescence reflectance imaging and fluorescence-mediated tomography up to 48 h after injection of the tracer. Binding specificity of the probe was demonstrated by predosing with PD156707 as a competing inhibitor. In conclusion, optical imaging with a fluorescent ETAR tracer allows the noninvasive imaging of tumor-associated ETAR expression in vivo. In the future, this technique may help surgeons to evaluate lesion dimensions in intraoperative settings (e.g. thyroidectomy).


2018 ◽  
Vol 109 (4) ◽  
pp. 912-918 ◽  
Author(s):  
Takeshi Imamura ◽  
Takashi Saitou ◽  
Ryosuke Kawakami

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