Isaiah J Fidler

..How has this field developed over the past century, and what major breakthroughs are most likely to lead to effective therapeutic approaches?..

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..These data demonstrate that targeting EGFR and VEGFR signaling on tumor-associated endothelial cells provides a viable approach for the treatment of colon cancer...

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..CONCLUSION: Inhibiting VEGF-R and EGF-R activation on tumor-associated endothelial cells with AEE788 combined with paclitaxel can bypass CaP cell resistance and prevent lymph node metastasis...

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..This heterogeneity in receptor expression among different tumor cells suggests that targeting a single tyrosine kinase may not yield eradication of the disease...

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..Our findings provide an additional explanation for the susceptibility of lung cancers to treatment with EGFR tyrosine kinase inhibitors...

..These data demonstrate that blockade of PDGF-R signaling pathways in tumor-associated stromal cells and pericytes inhibits the progressive growth and metastasis of colon cancer cells...

..6pl tumor cells was similar in all parabionts, the data clearly demonstrate a major role for host-derived MMP-9 in angiogenesis and in the growth of human pancreatic cancer in the pancreas of nude mice...

..Using STI571 to inhibit PDGF-R phosphorylation may, especially in combination with paclitaxel, produce substantial therapeutic effects against prostate cancer bone metastasis...

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..001), which was followed by apoptosis of tumor cells. CONCLUSION: Tumor-associated endothelial cells, rather than tumor cells themselves, appear to be the target for imatinib in prostate cancer bone metastasis...

..Men with high risk localized prostate cancer were treated with platelet derived growth factor receptor inhibitor therapy, docetaxel and hormone ablation in the preoperative setting, and clinicopathological outcomes were evaluated...

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..Knocking down IL-6 in tumor cells and decreasing TAMs was associated with the lowest incidences of bone tumors and lymph node metastasis. These results suggest that TAMs enhance the growth of prostate cancer cells in the bone...

..CONCLUSIONS: These data indicate that endothelial cells exposed to EGF produced by tumor cells express activated EGF-R and that targeting EGF-R can produce significant therapeutic effects against prostate cancer bone metastasis...

..Interfering with PDGFR signaling may be an approach to control the progressive growth of breast cancer cells and thus reduce bone lysis...

..These data show that TGF-beta2 expression by murine melanoma cells is necessary for the establishment and growth of metastases in the brain parenchyma...

..In conclusion, the expression of PDGF-Rbeta in stromal cells is influenced by the organ-specific microenvironment and is associated with metastatic potential...

..Collectively, these data demonstrate that blockade of phosphorylation of EGF-R and PDGF-R coupled with administration of paclitaxel significantly suppresses experimental human prostate cancer bone metastasis...

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..Hence, the immortalized cell line will be useful for studying the role of astrocytes in disease processes in the brain, such as metastasis...

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..Our data show that the interaction of EGFR-TKIs and chemotherapy is complex and suggest that other growth factors may activate the downstream signaling events...

..4 versus 37.8; P = 0.016). CONCLUSIONS: Combination therapy with paclitaxel and PKI166 prolongs survival in an orthotopic preclinical model of tongue cancer by increasing programmed cell death of oral cancer...

..These data suggest that investigations of the functional consequence of gene expression require accounting for experimental growth conditions...

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..The effectiveness of STI571 in our studies suggests targeting of PDGFRs as a novel treatment for osteosarcoma...

..Collectively, the data indicate that targeting activation of EGF-R on HRCC produces significant therapeutic benefits...

..Large multinucleated cells (MNCs) commonly exist in tumorigenic cancer cell lines that are used widely in research. However, the contributions of MNCs to tumorigenesis are unknown...

..These results suggest that blockade of either epidermal growth factor receptor or VEGF receptor signaling combined with chemotherapy provides an effective approach to the therapy of pancreatic cancer...

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..Collectively, these data suggest that expression of activated EGF-R by tumor-associated endothelial cells provides an important target for therapy...

..This combined therapy led to a significant reduction in tumor weight...

..Treatment of metastasis can be directed against tumor cells and/or microenvironmental factors that support tumor growth, such as tumor-associated blood vessels...

..We found no difference in the incidence of lung metastases produced by B16-BL6 melanoma cells growing exclusively within regional lymph nodes and cells growing within the pinna...

..Finally, combinatorial screenings on immortalized cells followed by in vivo targeting establishes an experimental framework for discovery and validation of additional ligand-directed pharmacodelivery systems...

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..Collectively, these data demonstrate that brain metastasis-associated microglia are derived from circulating mononuclear cells and exhibit selective and specific tumoricidal activity...

..These observations provide proof of principle for competitive cross-species hybridization of microarray experiments to characterize the effect of the microenvironment on tumor cell behavior...

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..The therapeutic combination of STI571 and Taxol may be a powerful tool for targeting tumor-associated endothelial cells in the skeletal compartment...

..Because PKI 166 prevented the activation of PI3K/Akt/NF-kappa B and MAPK(Erk) pathways, the combination of this tyrosine kinase inhibitor with gemcitabine should be an effective therapy for pancreatic cancer...

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..The immortalized endothelial cell lines established from H-2K(b)-tsA58 mice provide, for the first time, a cell culture system to examine factors regulating angiogenesis and tumor cell arrest in different organ systems...

..Collectively, these data show that blocking the phosphorylation of EGFR and VEGFR with AEE788 combined with paclitaxel can significantly inhibit experimental human FTC in the bone of nude mice...

..Our results indicate that MSCs may serve as a platform for delivery of biological agents in tumors...

..CONCLUSIONS: The administration of AEE788 and paclitaxel inhibits the progression of human ovarian carcinoma in the peritoneal cavity of female nude mice, in part, by inducing apoptosis of tumor-associated endothelial cells...

..The physiological role of astrocytes is to protect against neurotoxicity. Our current data demonstrate that activated astrocytes also protect tumor cells against chemotherapeutic drugs...

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..Collectively, these data suggest that the inhibition of AKT pathway due to loss of adhesion within the circulation renders a subpopulation of K-1735 cells to produce melanin...

..Our results also imply that TrkB receptor may be a novel therapeutic target for pancreatic cancer...

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..Collectively, these data demonstrate that Stat1 expressed by tumor cells is a negative regulator of tumor angiogenesis and, hence, tumor growth and metastasis...

..Clinical and translational data from these studies are likely to provide additional insights into the role of imatinib in combination therapy for prostate cancer...

..Collectively, the data suggest that combining the optimal biological dose of PEG-IFN-alpha with paclitaxel may provide a novel and effective approach to the treatment of human ovarian carcinoma...

..Then we correlated these data with patient clinical outcome...

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..Although the specificity of the marker for pancreatic cancer was low, it could be used to monitor the disease or to select high-risk patients with chronic pancreatitis...

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..The present data recommend the combination of a bisphosphonate agent with protein tyrosine kinase inhibitor and an anticycling drug for the treatment of prostate cancer bone metastasis...

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..Together, our findings suggest that ARD1 functions as an inhibitor of the mTOR pathway and that dysregulation of the ARD1-TSC2-mTOR axis may contribute to cancer development...

..In this review, we discuss how tumor-stromal interactions influence metastasis in each of these organs...

..The recent advances in our understanding of the biological basis of cancer metastasis present unprecedented possibilities for translating basic research to the clinical reality of cancer treatment...

..Collectively, the data indicate that ovarian tumor cells secreted IL-6, a highly angiogenic cytokine that supports progression of disease...

..Therapy of metastasis should therefore be targeted against both the metastatic tumor cells and the homeostatic factors that promote metastasis...

..The order of tumoricidal susceptibility of the B16 melanoma lines to activated macrophages was B16F1 > B16F10 > B16BL6, in inverse order of metastatic potential...

..Our goals were to (1) evaluate the toxicity and maximum-tolerated dose of docetaxel with imatinib, and (2) evaluate the decline of prostate-specific antigen (PSA) induced by imatinib alone, and imatinib and docetaxel...

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..We examined in vitro and in vivo effects of PKI166, an orally administered EGF-R inhibitor, on 2 human squamous cell carcinoma of the oral cavity cell lines, Tu159 and MDA1986...

..CONCLUSION: Host-derived MMP-9 expression, most likely in tumor-infiltrating macrophages, appears to play a critical role in angiogenesis and progressive growth of human ovarian tumors in mice...

..To analyze the molecular and cellular mechanisms of metastasis, we have developed an orthotopic nude mouse model of SCCOT...

..These data recommend the consideration of patients with head and neck cancer for inclusion in clinical trials of AEE788...

..Therapy of metastasis should therefore be targeted not only against tumor cells, but also against the host factors that contribute to and support the progressive growth and survival of metastatic cancer cells...

..Our data indicate that mesothelin-producing squamous cell carcinoma of the lung may be a good target for this immunotoxin...

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..These data suggest that the production of TGF-alpha by HRCC cells leads to the activation of EGFR on tumor-associated endothelial cells that serve as an essential target for therapy with tyrosine kinase inhibitors...

..This phase I study was conducted to assess the tolerability, pharmacokinetics, and antitumor activity of the oral, selective epidermal growth factor receptor tyrosine kinase inhibitor PKI166 in patients with advanced solid malignancies...

..Collectively, these data indicate that targeting PDGFR, Src, and Akt on tumor and tumor-associated endothelial cells may be an effective therapy for human pancreatic carcinoma...

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..The purpose of this study was to identify a mediator produced by human colon cancer cells that is responsible for the induction of hyperplasia in the adjacent mucosa...