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Clinical trials with antiangiogenic agents have not been able to validate plasma or serum levels of angiogenesis regulators as reliable markers of cancer presence or therapeutic response. We recently reported that platelets contain numerous proteins that regulate angiogenesis. We now show that accumulation of angiogenesis regulators in platelets of animals(More)
Tumor dormancy has important implications for early detection and treatment of cancer. Lack of experimental models and limited clinical accessibility constitute major obstacles to the molecular characterization of dormant tumors. We have developed models in which human tumors remain dormant for a prolonged period of time (>120 days) until they switch to(More)
Tumor dormancy is a highly prevalent stage in cancer progression. We have previously generated and characterized in vivo experimental models of human tumor dormancy in which micro-tumors remain occult until they spontaneously shift into rapid tumor growth. We showed that the dormant micro-tumors undergo a stable microRNA (miRNA) switch during their(More)
Dendritic cells (DCs)--immunomodulatory cells that initiate adaptive immune responses--have recently been shown to exert proangiogenic effects when infiltrating the tumor microenvironment. As tumors that escape immune surveillance inhibit DC maturation, we explored whether maturation status determines their ability to promote angiogenesis and whether(More)
BACKGROUND Microscopic human cancers can remain dormant for life. Tumor progression depends on sequential events, including a switch to the angiogenic phenotype, i.e., initial recruitment of new vessels. We previously demonstrated that human tumors contain tumor cell populations that are heterogeneous in angiogenic activity. Here, we separated angiogenic(More)
The present study shows that DNA damage induces different patterns of p53-dependent and p53-independent apoptosis in epithelial cells of various organs of adult mice. Genotoxic stress induced a biphasic apoptotic response in the small intestine and tongue. While the first immediate apoptotic wave was p53-dependent, the second was slower in rate and was(More)
Early tumor detection and intervention are important determinants of survival in patients with cancer. We have recently reported that the "platelet angiogenesis proteome" may be used to detect microscopic tumors in mice. We now present evidence that changes in platelet-associated platelet factor-4 (PF-4) detect malignant growth across a spectrum of human(More)
The ability to suppress wild type p53-independent apoptosis may play an important role in the oncogenicity of p53 mutant proteins. However, structural elements necessary for this activity are unknown. Furthermore, it is unclear whether this mutant p53 mediated inhibition is specific to the apoptotic pathway or a more general suppression of the cellular(More)
Upregulation of the p53 protein was shown to induce cell cycle arrest at the G1/S border and in some cases at the G2/M border. Furthermore, it was suggested that p53 is associated with the induction of the various DNA repair pathways. Previously, we demonstrated that cells co-expressing endogenous wild type p53 protein, together with dominant negative(More)