William R Cruz-Munoz

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Herein we report that the VEGFR/PDGFR kinase inhibitor sunitinib/SU11248 can accelerate metastatic tumor growth and decrease overall survival in mice receiving short-term therapy in various metastasis assays, including after intravenous injection of tumor cells or after removal of primary orthotopically grown tumors. Acceleration of metastasis was also(More)
An enduring problem in cancer research is the failure to reproduce highly encouraging preclinical therapeutic findings using transplanted or spontaneous primary tumours in mice in clinical trials of patients with advanced metastatic disease. There are several reasons for this, including the failure to model established, visceral metastatic disease. We(More)
Tissue inhibitors of metalloproteinases (TIMPs) are classically known for regulating members of the metzincin protease family and are well recognized for their inhibitory effects in cancer development and progression. Despite their common evolutionary structure, the four TIMP proteins have unique properties and regulation, and produce distinct phenotypes(More)
Metastatic spread of melanoma to the central nervous system (CNS) is a common and devastating manifestation of disease progression, which, despite its clinical importance, remains poorly understood with respect to underlying molecular mechanisms. Using a recently developed preclinical model of spontaneous melanoma CNS metastasis, we have identified(More)
Here, we report the first application and characterization of the cII locus as a mutational target for use with the Muta(trade mark)Mouse system for quantifying somatic mutations in vivo. This locus can be analyzed for mutations using positive selection and is identical in sequence to the cII in the Big Blue((R)) Mouse. The cII displays similar spontaneous(More)
Metastatic spread of melanoma to the central nervous system (CNS) is associated with dismal prognosis. Preclinical testing of novel therapeutic approaches would be aided by the development of appropriate models of spontaneous CNS metastasis arising from primary tumors. A highly metastatic variant of the WM239A human melanoma cell line, designated 113/6-4L,(More)
Low-dose metronomic chemotherapy has shown promising activity in many preclinical and some phase II clinical studies involving various tumor types. To evaluate further the potential therapeutic impact of metronomic chemotherapy for ovarian cancer, we developed a preclinical model of advanced human ovarian cancer and tested various low-dose metronomic(More)
PURPOSE The development of effective therapeutic approaches for treatment of metastatic melanoma remains an immense challenge. Present therapies offer minimal benefit. Although dacarbazine chemotherapy remains the standard therapy, it mediates only low response rates, usually of short duration, even when combined with other chemotherapeutic agents. Thus,(More)
Tumor cells, stromal cell compartment and the extracellular matrix (ECM) together generate a multifaceted tumor microenvironment. Matrix metalloproteinases and their tissue inhibitors (TIMPs) provide a means for tumor-stromal interaction during tumorigenesis. Among TIMPs, TIMP-3 is uniquely localized to the ECM and is frequently silenced in human cancers.(More)
Identifying versatile inhibitors of metastasis that operate in multiple sites against distinct cancer cell types is important for designing novel therapeutics for metastasis. We show that multiple tissues of timp-3-/- mice are more susceptible to metastatic colonization. Overall, a 5-14-fold increase in liver and kidney colonization occurred by EL-4(More)