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View the Table of Contents for the June 15 issue of Cancer Research.
Cheng et al. Page 4979
A small-molecule SPECT imaging probe (99mTc-1) was designed and evaluated in vitro and in vivo using melanoma mouse models by Cheng et al.99mTc-1 displayed high and specific tumor uptake in both subcutaneous and metastatic melanoma lesions. Tumor localization of 99mTc-1 in the metastatic lesions correlated with the tumor burden and its concentration increases as the metastatic lesions grow. This small technetium-complex may have potential clinical utility not only in the diagnostic imaging of metastatic spread of melanotic melanoma but also as an imaging probe to evaluate the efficacy of various therapeutic regimens in murine models of metastatic melanoma.
Huang et al. Page 5009
The mechanisms by which tumor cells escape from immune surveillance are incompletely understood. Huang et al. have demonstrated that toll like receptors (TLRs), thought to be restricted to immune cells, are widely expressed in tumors. Activation of the TLR4 signal pathway in tumors triggers the expression of various factors/molecules that are important for tumor cell immune evasion. Furthermore, blockade of TLR4 signal pathway reverses tumor-mediated immune suppression and results in the prolonged survival of tumor-bearing mice. These studies open a new aspect of tumor biology and may lead to discovery of new therapeutic targets in cancer therapy.
Lu et al. Page 5015
Vascular endothelial growth factor (VEGF) plays a crucial role in angiogenesis. Tumor-induced angiogenesis has been associated with cancer progression and metastasis. The VEGF gene is highly polymorphic. The effect of functional polymorphisms in the VEGF gene on breast cancer prognosis, however, has not been previously investigated. Lu et al. evaluated the association of three functional polymorphisms (G+405C, C–460T, and C+936T) in the VEGF gene with breast cancer survival in a cohort of 1,193 breast cancer patients who were followed for 4.8 years. The study showed that carrying the +405G or the –460C allele or the –460T/+450C/+936C haplotype was associated with a decreased survival after cancer diagnosis. The genotype and survival associations persisted after adjustment for known breast cancer prognostic factors. This study suggests that VEGF polymorphisms may be a significant genetic marker for breast cancer prognosis.
Le Calvez et al. Page 5076
TP53 mutations are common in lung cancers of smokers and often show a high prevalence of transversions at specific guanines. This mutation pattern has been interpreted as a molecular “signature” of mutagenesis by tobacco carcinogens, including, in particular, derivatives of polycyclic aromatic hydrocarbons such as benzo(a)pyrene. Le Calvez et al. demonstrate that TP53 mutation patterns in lung cancers are different in current, former, and ex-smokers. In current smokers, mutations often fall at codons encoding residues at the outer surface of the p53 protein, suggesting a common structural and functional effect. In never smokers, tumors often contain high levels of nitrotyrosine, a marker of protein damage by inflammation-related reactive nitrogen species. These results further support the emerging notion that lung tumorigenesis proceeds through different molecular mechanisms according to smoking status.
Hallak et al. Page 5292
Integrin αvβ3 is expressed on certain tumor cells and on dividing endothelial cells which form a physical barrier against therapeutics that are directed to tumors from the blood stream. To break this barrier, Hallak et al. generated a targeted oncolytic measles virus, MV-ERV, displaying echistatin that has a high affinity to integrin αvβ3. The vector’s binding to native CD46 receptor was retained to allow infection of tumor cells after breaking the endothelial barrier. The vector showed high specificity and led to reduction or eradication of multiple myeloma tumor xenografts in animals. This strategy is a promising approach for targeting solid tumors.