Effect of prolonged coumadin treatment on the production of pulmonary metastases in the rat

Agostino, Domenico; Cliffton, Eugene E.; Girolami, Antonio

doi:10.1002/1097-0142(196602)19:2<284::aid-cncr2820190223>3.0.co;2-0

Cited by 31 publications

(14 citation statements)

References 14 publications

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“…Inhibition of metastasis was essentially complete, with a 99.9% reduction in the number of lung lesions in treated mice. Although pharmacologic inhibitors of coagulation such as heparin, LMWHs, or hirudin, have been shown to inhibit metastasis in tail vein models,33, 34, 35, 36, 37, 38, 39 and murine anti‐hTF antibodies26 have been used in experimental melanoma metastasis models, this is the first demonstration that a function blocking human antibody can inhibit experimental breast cancer metastasis to the lung.…”

Section: Discussionmentioning

confidence: 96%

CNTO 859, a humanized anti‐tissue factor monoclonal antibody, is a potent inhibitor of breast cancer metastasis and tumor growth in xenograft models

Ngo¹,

Picha²,

McCabe³

et al. 2006

Intl Journal of Cancer

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Thromboembolic complications are frequently associated with advanced cancer. Interestingly, one of the major initiators of blood coagulation, tissue factor (TF), is reported to be overexpressed in several tumor types and can be found on both tumor cells and tumor vasculature. Although the exact mechanisms have yet to be elucidated, TF expressed on tumor cells can trigger intracellular signaling events through various pathways that can lead to tumor angiogenesis, proliferation, and metastasis. There exists preclinical evidence that disruption of TF dependent signaling can effectively inhibit tumor cell migration, metastasis, and angiogenesis. Here, we report for the first time that an antibody to tissue factor can also prevent tumor growth in vivo. Prophylactic administration of CNTO 859, a humanized anti-human TF antibody, was shown to inhibit experimental lung metastasis of MDA-MB-231 human breast carcinoma cells by over 99% compared to a control antibody. Furthermore, therapeutic doses of CNTO 859 were shown to reduce tumor incidence and growth of orthotopically implanted MDA-MB-231 cells. ' 2006 Wiley-Liss, Inc.

show abstract

Section: Discussionmentioning

confidence: 96%

CNTO 859, a humanized anti‐tissue factor monoclonal antibody, is a potent inhibitor of breast cancer metastasis and tumor growth in xenograft models

Ngo¹,

Picha²,

McCabe³

et al. 2006

Intl Journal of Cancer

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show abstract

“…In this approach, all patients were initially considered as non-users and then users after a lag of 6 months following their first warfarin prescription. Effect estimates are presented unadjusted and then adjusted for each cancer site d Analysis was restricted to first-time users ('new starts') of warfarin therapy post-diagnosis [36][37][38]. Given this biological plausibility, it is noteworthy that the weak non-significant reductions observed for ever versus never warfarin users among breast and colorectal cancer patients in the current analysis may have resulted from low statistical power.…”

Section: Discussionmentioning

confidence: 98%

The effect of warfarin therapy on breast, colorectal, lung, and prostate cancer survival: a population-based cohort study using the Clinical Practice Research Datalink

O’Rorke

Murray

Hughes

et al. 2014

Cancer Causes Control

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“…Many tumor cells express abnormal levels of procoagulants, mainly tissue factor (TF) and cancer procoagulant [2, 3], which are assumed to be responsible for the prothrombotic phenotype. Animal experiments indicate that anticoagulant therapy may reduce metastasis [4–6], and clinical studies in cancer patients suggest that such treatment may prolong survival [7]. Importantly, many cancer patients have been found to express elevated levels of the coagulation inhibitor TF pathway inhibitor (TFPI) [8, 9] which may be an important protective effect in these patients [10].…”

Section: Introductionmentioning

confidence: 99%

Overexpression of both TFPIα and TFPIβ induces apoptosis and expression of genes involved in the death receptor pathway in breast cancer cells

Stavik

Skretting

Sletten

et al. 2010

Molecular Carcinogenesis

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Thrombosis is a major complication and an important cause of death in cancer patients. Tumor cells may trigger coagulation and induce a prothrombotic phenotype, which in return may enhance angiogenesis, tumor growth, and metastasis. Tissue factor pathway inhibitor (TFPI) has been reported to reduce tumor growth and metastasis in vivo and to induce apoptosis and inhibit proliferation in normal cells in vitro. However, no effect has so far been observed in cancer cells. We therefore aimed to characterize the functional effects of ectopic overexpression and endogenous downregulation of TFPI in cancer cells, and to elucidate possible mechanisms involved. The tumor derived breast cancer cells SK-BR-3 and Sum102 were used to construct stable cell lines overexpressing TFPIα and TFPIβ, and with TFPI knocked down, respectively. Effects of altered TFPI expression were evaluated by measuring apoptosis and proliferation of the cells, and gene expressions were analyzed using PCR arrays. Increased DNA fragmentation and Caspase 3 activity was observed in SK-BR-3 cells overexpressing TFPIα and TFPIβ, while a decrease in apoptosis was seen in Sum102 cells with TFPI expression knocked down. An increase and reduction in expression of pro- and anti-apoptotic genes, respectively, were seen in TFPI overexpressing cells, and the majority of the upregulated genes encoded proteins involved in the death receptor pathway, among them the death receptor ligand TNF-α. In conclusion, TFPIα and TFPIβ induced apoptosis in breast cancer cells and increased expression of apoptotic genes indicating a possible involvement of the death receptor pathway.

show abstract

Effect of prolonged coumadin treatment on the production of pulmonary metastases in the rat

Cited by 31 publications

References 14 publications

CNTO 859, a humanized anti‐tissue factor monoclonal antibody, is a potent inhibitor of breast cancer metastasis and tumor growth in xenograft models

CNTO 859, a humanized anti‐tissue factor monoclonal antibody, is a potent inhibitor of breast cancer metastasis and tumor growth in xenograft models

The effect of warfarin therapy on breast, colorectal, lung, and prostate cancer survival: a population-based cohort study using the Clinical Practice Research Datalink

Overexpression of both TFPIα and TFPIβ induces apoptosis and expression of genes involved in the death receptor pathway in breast cancer cells

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