Tissue factor expression as a possible determinant of thromboembolism in ovarian cancer

Uno, Kiyoko; Homma, Shinsuke; Satoh, Toyomi; Nakanishi, Kyoko; Asaoka, Daisuke; Matsumoto, Koji; Oki, Akinori; Tsunoda, Hajime; Yamaguchi, Iwao; Nagasawa, Toshiro; Yoshikawa, Hiroyuki; Aonuma, Kazutaka

doi:10.1038/sj.bjc.6603552

Cited by 164 publications

(128 citation statements)

References 29 publications

(29 reference statements)

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“…Two recent studies have shown that tissue factor (TF) expression by tumor cells may be predictive of systemic VTE in patients with pancreatic and ovarian cancer (50,51). Tumor cells in HCC also have been shown to express TF (52,53).…”

Section: Discussionmentioning

confidence: 99%

Incidence, risk factors and consequences of portal vein and systemic thromboses in hepatocellular carcinoma

Connolly

Chen

Hyrien

et al. 2008

Thrombosis Research

105

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Section: Discussionmentioning

confidence: 99%

Incidence, risk factors and consequences of portal vein and systemic thromboses in hepatocellular carcinoma

Connolly

Chen

Hyrien

et al. 2008

Thrombosis Research

105

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“…In the present study, clear cell histology was a risk factor for both preoperative silent DVT and PTE in ovarian cancer patients. Very recently, we used immunohistochemical methods to reveal that clear cell adenocarcinoma shows significantly stronger expression of tissue factor, a major factor in the procoagulant activities of cancer cells, compared to nonclear cell adenocarcinoma (Uno et al, 2007). Massive ascites was also an independent and significant risk factor for preoperative DVT in ovarian cancer.…”

Section: Thromboembolism In Ovarian Cancer T Satoh Et Almentioning

confidence: 99%

High incidence of silent venous thromboembolism before treatment in ovarian cancer

et al. 2007

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Venous thromboembolism (VTE) such as deep-vein thrombosis (DVT) and pulmonary thromboembolism (PTE) often occurs after surgery and rarely occurs even before surgery in patients with ovarian cancer. It is well known that levels of plasma D-dimer (DD) before treatment in most ovarian cancer patients are increased. This study therefore examined whether increased levels of DD are associated with presence of VTE before treatment of ovarian cancer. Between November 2004 and March 2007, DD levels prior to initial treatment were measured in 72 consecutive patients with presumed epithelial ovarian cancer (final diagnosis: epithelial ovarian cancer, n ¼ 60; and epithelial ovarian borderline malignancy, n ¼ 12). Venous ultrasound imaging (VUI) of the lower extremity was conducted for all patients except for two patients in whom DVT was detected by pelvic computed tomography (CT). When DVT was found, pulmonary scintigraphy was subsequently performed to ascertain presence of PTE. D-dimer levels were above the cut-off value (0.5 mg ml À1 ) in 65 of 72 patients (90.2%). Venous ultrasound imaging or CT revealed DVT in 18 of 72 patients (25.0%) and pulmonary scintigraphy found PTE in 8 patients (11.1%). All patients with VTE were asymptomatic when VTE was found. D-dimer levels were associated with incidence of VTE (0 -1.4 mg ml À1 ; 0 of 26 (0%), 1.5 -7.4 mg ml À1 ; 9 of 30 (30%) and X7.5 mg ml À1 ; 9 of 16 (56.3%), P for trend ¼ 0.0003). However, even if 1.5 mg ml À1 was used as a cut-off value, this had low specificity and positive predictive value (47.2, 38.3%), though it had high sensitivity and negative predictive value (100, 100%). Therefore, ovarian cancer patients with DD level X1.5 mg ml À1 should be examined using VUI to detect silent DVT. Patients with VTE underwent preventive managements including anticoagulant therapy before initial treatment, chemotherapy or surgery, and after surgery. There was no clinical onset of postoperative VTE in all 72 patients. Measurement of DD levels and subsequent ultrasonography revealed that silent or subclinical VTE frequently occurs before surgery in ovarian cancer. The usefulness of preoperative assessment of VTE needs further confirmation in randomised controlled trials.

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“…TF, also called thromboplastin, factor III, or CD142, is aberrantly expressed in many types of cancers, including non-small cell lung cancer (5), colorectal cancer (6), genito-urethal (7,8), and gynecologic cancers (9)(10)(11), pancreatic cancer (12), head and neck cancer (13), glioma (14), and metastatic breast cancer (15). Under physiologic conditions, TF is expressed by fibroblasts, pericytes, and smooth muscle cells in the subendothelial vessel wall.…”

Section: Introductionmentioning

confidence: 99%

High Turnover of Tissue Factor Enables Efficient Intracellular Delivery of Antibody–Drug Conjugates

Goeij

Satijn

Freitag

et al. 2015

Molecular Cancer Therapeutics

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Antibody-drug conjugates (ADC) are emerging as powerful cancer treatments that combine antibody-mediated tumor targeting with the potent cytotoxic activity of toxins. We recently reported the development of a novel ADC that delivers the cytotoxic payload monomethyl auristatin E (MMAE) to tumor cells expressing tissue factor (TF). By carefully selecting a TFspecific antibody that interferes with TF:FVIIa-dependent intracellular signaling, but not with the procoagulant activity of TF, an ADC was developed (TF-011-MMAE/HuMax-TF-ADC) that efficiently kills tumor cells, with an acceptable toxicology profile. To gain more insight in the efficacy of TF-directed ADC treatment, we compared the internalization characteristics and intracellular routing of TF with the EGFR and HER2. Both in absence and presence of antibody, TF demonstrated more efficient internalization, lysosomal targeting, and degradation than EGFR and HER2. By conjugating TF, EGFR, and HER2-specific antibodies with duostatin-3, a toxin that induces potent cytotoxicity upon antibody-mediated internalization but lacks the ability to induce bystander killing, we were able to compare cytotoxicity of ADCs with different tumor specificities. TF-ADC demonstrated effective killing against tumor cell lines with variable levels of target expression. In xenograft models, TF-ADC was relatively potent in reducing tumor growth compared with EGFR-and HER2-ADCs. We hypothesize that the constant turnover of TF on tumor cells makes this protein specifically suitable for an ADC approach.

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Tissue factor expression as a possible determinant of thromboembolism in ovarian cancer

Cited by 164 publications

References 29 publications

Incidence, risk factors and consequences of portal vein and systemic thromboses in hepatocellular carcinoma

Incidence, risk factors and consequences of portal vein and systemic thromboses in hepatocellular carcinoma

High incidence of silent venous thromboembolism before treatment in ovarian cancer

High Turnover of Tissue Factor Enables Efficient Intracellular Delivery of Antibody–Drug Conjugates

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