May 15 Cancer Research Highlights

Selected Articles from the May 15, 2009 Issue

The articles referenced in this Highlights section will be available online in HTML and PDF formats to all interested users at no charge until the next issue of Cancer Research is published. Click on the article title to view the complete article.

View the Table of Contents for the May 15 issue of Cancer Research.

Mesenchymal Stem Cell Delivery of TRAIL Can Eliminate Metastases

Loebinger et al.

Page 4134

Mesenchymal stem cells (MSCs) have been shown to preferentially home to tumors, and this characteristic can be used for directed cancer therapy. Loebinger and colleagues used lentiviral vectors to express TRAIL on the surface of MSCs under the tight control of doxycycline. Using murine models, the authors show that therapy with these engineered MSCs can both reduce the growth of subcutaneous tumors and inhibit the development of lung metastases. This study adds to previous work using MSCs as vectors, and the demonstration of the elimination of metastases has clear future therapeutic potential as adjuvant therapy following primary tumor resection.

Efficacy of an Aurora B Inhibitor in Leukemic Stem Cells

Oke et al.

Page 4150

Aurora kinases are involved in regulating mitosis and cytokinesis and have been implicated in the survival and proliferation of both hematologic and solid malignancies. The selective aurora B kinase inhibitor AZD1152 has been shown to significantly inhibit tumor growth in a variety of solid tumor xenograft models and is in early clinical evaluation. Oke and colleagues evaluated the effects of AZD1152 on acute myeloid leukemia (AML) in vitro and in vivo and report that AZD1152 had a cytotoxic effect on all AML cell lines studied and inhibited phosphorylation of histone H3 in a dose-dependent manner. AZD1152 also inhibited growth in a xenotransplantation model. These data suggest that the inhibition of aurora B kinase may be a useful therapeutic strategy in the therapy of AML.

Multiparameter Computational Modeling of Tumor Invasion

Bearer et al.

Page 4493

Bearer and colleagues apply a mathematical model of tumor growth to show that tumor growth and invasion are governed by biophysical laws. Using the model, the authors identify functional relationships linking genetic and phenotypic effects, the microenvironment, growth, and morphology. For different values of parameters, the model predicts invasion via individual cells, cell chains, and strands or detached clusters, as observed in experiments and histopathology, and that these infiltration morphologies correspond to different stages of progression regulated by cellular and microenvironment heterogeneity. These data suggest that this model can be used for the quantitative study of tumor progression as well as diagnostic and prognostic applications.

Hypoxic Glioblastomas Are Quantitatively More Aggressive

Szeto et al.

Page 4502

Glioblastoma multiforme are aggressive brain tumors and hypoxia is a common hallmark of aggressive tumor behavior, important for its impact on treatment sensitivity. Magnetic resonance imaging (MRI) and positron emission tomography (PET) offer noninvasive means to provide anatomic tumor information and target hypoxia, respectively. In a study of newly diagnosed glioblastomas, Szeto and colleagues show that a biomathematical model for glioma growth and invasion provides a means of dynamically quantifying an in vivo link between biological aggressiveness assessed by serial routine MRI and hypoxia assessed with ¹⁸F-fluoromisonidazole (FMISO)–PET. The authors show that the more aggressive tumors had a larger hypoxic burden. These data establish a quantitative link between biological aggressiveness assessed by combining serial MRI with a biomathematical model for glioma growth and invasion.

PET Imaging of Tumor Extracellular pH

Vavere et al.

Page 4510
Vavere et al.

Solid tumors often develop an acidic environment and the effectiveness of diagnosis and therapy may be enhanced by the design and use of pH-sensitive agents that target acidic tumors. Recently, a novel technology was introduced to target acidic tumors using pH low insertion peptide (pHLIP), a peptide that inserts across cell membranes when the extracellular pH is acidic. Vavere and colleagues expanded the application of the pHLIP technology to include positron emission tomography (PET) imaging of the acidic environment in prostate tumors using ⁶⁴Cu-DOTA-pHLIP. Uptake correlated with differences in the bulk extracellular pH of PC-3 and LNCaP tumors measured in magnetic resonance spectroscopy experiments. This study introduces a novel class of noninvasive pH-selective PET imaging agents and opens new research directions in the diagnosis of acidic solid tumors.

May 15 Cancer Research Highlights

Selected Articles from the May 15, 2009 Issue

Mesenchymal Stem Cell Delivery of TRAIL Can Eliminate Metastases

Efficacy of an Aurora B Inhibitor in Leukemic Stem Cells

Multiparameter Computational Modeling of Tumor Invasion

Hypoxic Glioblastomas Are Quantitatively More Aggressive

PET Imaging of Tumor Extracellular pH

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