In vivo imaging to initialize a biophysical model of tumor growth: Preliminary results

Author(s):  
David A. Hormuth ◽  
Thomas E. Yankeelov
2006 ◽  
Vol 348 (3) ◽  
pp. 997-1002 ◽  
Author(s):  
Maja Cemazar ◽  
Muriel Golzio ◽  
Jean-Michel Escoffre ◽  
Bettina Couderc ◽  
Gregor Sersa ◽  
...  
Keyword(s):  

2020 ◽  
pp. 1-11
Author(s):  
Naoki Fukui ◽  
Toshio Yawata ◽  
Takahito Nakajo ◽  
Yu Kawanishi ◽  
Youichirou Higashi ◽  
...  

OBJECTIVEGlioma stem cells (GSCs) are responsible for tumor initiation, therapeutic resistance, and recurrence. CD146 is mainly expressed in dividing GSCs and regulates cell cycle progression. However, the evaluation of the efficacy of targeted therapy against CD146 in vivo remains to be investigated. In this study, the authors aimed to develop gene therapy targeting GSCs using chitosan oligosaccharide lactate (COL) nanoparticles (NPs) conjugated with folic acid–polyethylene glycol (FA-PEG-COL NPs) for in vitro and in vivo delivery of CD146 small-interfering RNA (siCD146) and to determine the effect of CD146 knockdown on tumor growth.METHODSTo examine the uptake of NPs by tumor cells, immunofluorescence staining, flow cytometry, and in vivo imaging were performed. The knockdown effect of siCD146 was measured by western blot and water-soluble tetrazolium salt–8 assay in mouse glioma cells. The efficacy of siRNA therapy–targeted GSCs was evaluated by monitoring tumor growth through in vivo imaging and histological analysis.RESULTSIn vivo accumulation of the FA-PEG-COL NPs in subcutaneous and intracranial gliomas following NP administration via a mouse tail vein was observed. Additionally, in vitro delivery of siCD146 ionically cross-linked NPs, reduced CD146 levels, and suppressed growth in the glioma tumor sphere. Evaluation of the in vivo therapeutic effects of siCD146–cross-linked NPs in a mouse glioma model revealed significant suppression of intracranial tumor growth, with complete removal of the tumor observed in some mice on histological examination. Furthermore, delivery of siCD146 significantly reduced the Ki-67 index in residual tumor tissues relative to that in control mice.CONCLUSIONSCD146 is a potential therapeutic target, and folic acid–conjugated NPs delivering siRNA may facilitate gene therapy in malignant gliomas.


2017 ◽  
Author(s):  
Anthony Phan ◽  
Karol Karnowski ◽  
Qingyun Lee ◽  
Peter Fejes ◽  
Bryden Quirk ◽  
...  

2011 ◽  
Author(s):  
Myron S. Ignatius ◽  
Eleanor Chen ◽  
Natalie Elpek ◽  
Petur Nielsen ◽  
Corinne Linardic ◽  
...  

2010 ◽  
Vol 13 (6) ◽  
pp. 369-376 ◽  
Author(s):  
Serge G. Rosolen ◽  
Barbara Lamory ◽  
Fabrice Harms ◽  
José-Alain Sahel ◽  
Serge Picaud ◽  
...  

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2805-2805
Author(s):  
Angela Colmone ◽  
Veena Krishnamoorthy ◽  
Dorothy A. Sipkins

Abstract Tissue microenvironments have been shown to critically regulate cancer cell survival and proliferation. Conversely, while tumor growth can induce neovascularization, the impact of other tumor-induced changes in the microenvironment are less well understood. Here we utilize a xenograft model of Nalm-6 pre-B acute lymphoblastic leukemia (ALL) in SCID mice to examine how tumor growth alters the bone marrow (BM) microenvironment. Using dynamic confocal and multiphoton in vivo imaging, we find that tumor growth dramatically down-regulates expression of the chemokine SDF-1 in the BM microvasculature in areas of leukemic proliferation. SDF-1 has been shown to play a key role in cancer cell metastasis for numerous cell types including Nalm-6, and directs initial Nalm-6 homing to specific SDF-1-positive vascular beds. In contrast, we found that Nalm-6 introduced in mice previously engrafted with leukemia home to SDF-1-negative vasculature, predominantly at the advancing tumor margin. Furthermore, inhibition of chemokine signaling by pertussis toxin pre-treatment of Nalm-6 cells demonstrates that Nalm-6 homing in engrafted mice is chemokine-independent. In summary, these findings suggest that leukemic growth profoundly alters the mechanisms underlying the metastatic process by inducing changes in the host vascular microenvironment. These changes may increase the efficiency of the metastatic process and/or the advancement of the tumor margin. Therapies directed at blocking tumor metastases, therefore, may need to be tailored according to tumor stage.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10072-10072
Author(s):  
Hiroaki Kimura ◽  
Yasunori Tome ◽  
Masashi Momiyama ◽  
Katsuhiro Hayashi ◽  
Michael Bouvet ◽  
...  

10072 Background: Integrins play a role in tumor growth and metastasis (Int. J. Cancer 129, 2905-2915, 2011). However, the effect of integrin inhibition has not been visualized on single cancer cells in vivo. In this study, we used a powerful subcellular in vivo imaging model to demonstrate how an anti-integrin antibody affects seeding and growth of osteosarcoma cells on the lung. Methods: The 143B human osteosarcoma cell line expressing red fluorescent protein (RFP) in the cytoplasm and green fluorescent protein (GFP) in the nucleus was established. Using the double-labeled osteosarcoma cells, single cancer-cell seeding in the lung after i.v. injection of osteosarcoma cells was imaged in live mice. Results: The anti-b1 integrin monoclonal antibody, AIIB2, greatly inhibited the seeding of cancer cells on the lung while a control antibody had no effect. To image the efficacy of the anti-integrin antibody on spontaneous metastasis, mice with orthotopically-growing 143B-RFP cells in the tibia were also treated with AIIB2 or control anti-rat IgG1 antibody. After 3 weeks treatment, mice were sacrificed and primary tumors and lung metastases were evaluated with fluorescence imaging. AIIB2 significantly inhibited spontaneous lung metastasis but not primary tumor growth. In a separate experiment, the anti-β1 integrin antibody increased survival in the orthothopic osteosarcoma model. Conclusions: The efficacy of the anti-β1 integrin antibody against metastasis may be due to inhibition of lung seeding of the cancer cells. The increased survival of mice with orthotopically-growing 143B-RFP treated with AIIB2 may be due to inhibition of metastasis, which in turn may be inhibited by effect of the anti-β1 integrin on cancer-cell seeding in the lung.


2013 ◽  
Vol 185 (1) ◽  
pp. 143-151 ◽  
Author(s):  
Andreas Thalheimer ◽  
Doreen Korb ◽  
Lars Bönicke ◽  
Armin Wiegering ◽  
Bettina Mühling ◽  
...  

2017 ◽  
Vol 19 (suppl_6) ◽  
pp. vi23-vi23 ◽  
Author(s):  
David Hormuth ◽  
Angela Jarrett ◽  
Xinzeng Feng ◽  
Thomas Yankeelov

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