Antivascular effects of combretastatin A4 phosphate in breast cancer xenograft assessed using dynamic bioluminescence imaging and confirmed by MRI

Zhao, Dawen; Richer, Edmond; Antich, Peter P.; Mason, Ralph P.

doi:10.1096/fj.07-103713

Cited by 56 publications

(86 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To determine if high levels of peripheral shell cross-linking increase the potency of physically loaded CA4 in primary breast tumors after IV administration, we compared the extent that CA4 in X-F127 PM (22.9 wt%) affect the vascular function and subsequent growth of primary murine breast tumors that stably express luciferase (4T1-Luc) to CA4 in F127 PM (22.9 wt%), water-soluble CA4 phosphate (CA4P) (42), or PBS by an IVIS-based assay (33) and monitoring tumor volumes, respectively (Fig.10). X-F127 PM increased vascular shutdown by CA4 58% over PBS after 2 hours [68 ± 1 (SD) vs. 10 ± 2%, P < 0.0001], whereas F127 PM increased shutdown by only 10% over PBS [20 ± 2 (SD) vs. 10 ± 2%, P = 0.007], and CA4P had no effect [20 ± 2 (SD) vs. 10 ± 2%, P = 0.5901] (Fig.10A, open bars).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Peripherally Cross-Linking the Shell of Core-Shell Polymer Micelles Decreases Premature Release of Physically Loaded Combretastatin A4 in Whole Blood and Increases its Mean Residence Time and Subsequent Potency Against Primary Murine Breast Tumors After IV Administration

Wakaskar¹,

Bathena²,

Tallapaka³

et al. 2014

Pharm Res

View full text Add to dashboard Cite

Purpose Determine the feasibility and potential benefit of peripherally cross-linking the shell of core-shell polymer micelles on the premature release of physically loaded hydrophobic drug in whole blood and subsequent potency against solid tumors. Methods Individual Pluronic F127 polymer micelles (F127 PM) peripherally cross-linked with ethylenediamine at 76% of total PEO blocks (X-F127 PM) were physically loaded with combretastatin A4 (CA4) by the solid dispersion method and compared to CA4 physically loaded in uncross-linked F127 PM, CA4 in DMSO in vitro, or water-soluble CA4 phosphate (CA4P) in vivo. Results X-F127 PM had similar CA4 loading and aqueous solubility as F127 PM up to 10 mg CA4 / mL at 22.9 wt% and did not aggregate in PBS or 90% (v/v) human serum at 37°C for at least 24 h. In contrast, X-F127 PM decreased the unbound fraction of CA4 in whole blood (fu) and increased the mean plasma residence time and subsequent potency of CA4 against the vascular function and growth of primary murine 4T1 breast tumors over CA4 in F127 PM and water-soluble CA4P after IV administration. Conclusions Given that decreasing the fu is an indication of decreased drug release, peripherally cross-linking the shell of core-shell polymer micelles may be a simple approach to decrease premature release of physically loaded hydrophobic drug in the blood and increase subsequent potency in solid tumors.

show abstract

Section: Resultsmentioning

confidence: 99%

“…The extent of vascular shutdown and growth inhibition of primary tumors was determined by an IVIS-based method (33) and monitoring tumor volumes, respectively. 4T1 cells stably expressing luciferase (4T1-Luc) (34) were injected s.q.…”

Section: Methodsmentioning

confidence: 99%

Peripherally Cross-Linking the Shell of Core-Shell Polymer Micelles Decreases Premature Release of Physically Loaded Combretastatin A4 in Whole Blood and Increases its Mean Residence Time and Subsequent Potency Against Primary Murine Breast Tumors After IV Administration

Wakaskar¹,

Bathena²,

Tallapaka³

et al. 2014

Pharm Res

View full text Add to dashboard Cite

show abstract

“…D-luciferin is non-toxic and has been shown to be capable of penetrating intact blood-brain barrier (BBB) and cell membranes 3,5 .…”

Section: In Vivo Bioluminescence Imaging Of Tumor Hypoxia Dynamics Inmentioning

confidence: 99%

<em>In vivo</em> Bioluminescence Imaging of Tumor Hypoxia Dynamics of Breast Cancer Brain Metastasis in a Mouse Model

Saha

Dunn

Zhou

et al. 2011

JoVE

Self Cite

View full text Add to dashboard Cite

It is well recognized that tumor hypoxia plays an important role in promoting malignant progression and affecting therapeutic response negatively. There is little knowledge about in situ, in vivo, tumor hypoxia during intracranial development of malignant brain tumors because of lack of efficient means to monitor it in these deep-seated orthotopic tumors. Bioluminescence imaging (BLI), based on the detection of light emitted by living cells expressing a luciferase gene, has been rapidly adopted for cancer research, in particular, to evaluate tumor growth or tumor size changes in response to treatment in preclinical animal studies. Moreover, by expressing a reporter gene under the control of a promoter sequence, the specific gene expression can be monitored non-invasively by BLI. Under hypoxic stress, signaling responses are mediated mainly via the hypoxia inducible factor-1α (HIF-1α) to drive transcription of various genes. Therefore, we have used a HIF-1α reporter construct, 5HRE-ODD-luc, stably transfected into human breast cancer MDA-MB231 cells (MDA-MB231/5HRE-ODD-luc). In vitro HIF-1α bioluminescence assay is performed by incubating the transfected cells in a hypoxic chamber (0.1% O2) for 24 hr before BLI, while the cells in normoxia (21% O2) serve as a control. Significantly higher photon flux observed for the cells under hypoxia suggests an increased HIF-1α binding to its promoter (HRE elements), as compared to those in normoxia. Cells are injected directly into the mouse brain to establish a breast cancer brain metastasis model. In vivo bioluminescence imaging of tumor hypoxia dynamics is initiated 2 wks after implantation and repeated once a week. BLI reveals increasing light signals from the brain as the tumor progresses, indicating increased intracranial tumor hypoxia. Histological and immunohistochemical studies are used to confirm the in vivo imaging results. Here, we will introduce approaches of in vitro HIF-1α bioluminescence assay, surgical establishment of a breast cancer brain metastasis in a nude mouse and application of in vivo bioluminescence imaging to monitor intracranial tumor hypoxia. Video LinkThe video component of this article can be found at

show abstract

“…Dynamic BLI has been employed for tumor drug development to study their effect on the neoplastic cells. 226 …”

Section: Optical Imaging Techniquesmentioning

confidence: 99%

Whole animal imaging

Sandhu

Solorio

Broome

et al. 2010

WIREs Mechanisms of Disease

View full text Add to dashboard Cite

Translational research plays a vital role in understanding the underlying pathophysiology of human diseases, and hence development of new diagnostic and therapeutic options for their management. After creating an animal disease model, pathophysiologic changes and effects of a therapeutic intervention on them are often evaluated on the animals using immunohistologic or imaging techniques. In contrast to the immunohistologic techniques, the imaging techniques are noninvasive and hence can be used to investigate the whole animal, oftentimes in a single exam which provides opportunities to perform longitudinal studies and dynamic imaging of the same subject, and hence minimizes the experimental variability, requirement for the number of animals, and the time to perform a given experiment. Whole animal imaging can be performed by a number of techniques including x-ray computed tomography, magnetic resonance imaging, ultrasound imaging, positron emission tomography, single photon emission computed tomography, fluorescence imaging, and bioluminescence imaging, among others. Individual imaging techniques provide different kinds of information regarding the structure, metabolism, and physiology of the animal. Each technique has its own strengths and weaknesses, and none serves every purpose of image acquisition from all regions of an animal. In this review, a broad overview of basic principles, available contrast mechanisms, applications, challenges, and future prospects of many imaging techniques employed for whole animal imaging is provided. Our main goal is to briefly describe the current state of art to researchers and advanced students with a strong background in the field of animal research.

show abstract

Antivascular effects of combretastatin A4 phosphate in breast cancer xenograft assessed using dynamic bioluminescence imaging and confirmed by MRI

Cited by 56 publications

References 34 publications

Peripherally Cross-Linking the Shell of Core-Shell Polymer Micelles Decreases Premature Release of Physically Loaded Combretastatin A4 in Whole Blood and Increases its Mean Residence Time and Subsequent Potency Against Primary Murine Breast Tumors After IV Administration

Peripherally Cross-Linking the Shell of Core-Shell Polymer Micelles Decreases Premature Release of Physically Loaded Combretastatin A4 in Whole Blood and Increases its Mean Residence Time and Subsequent Potency Against Primary Murine Breast Tumors After IV Administration

<em>In vivo</em> Bioluminescence Imaging of Tumor Hypoxia Dynamics of Breast Cancer Brain Metastasis in a Mouse Model

Whole animal imaging

Contact Info

Product

Resources

About