Evaluation of venous thrombosis and tissue factor in epithelial ovarian cancer

Cohen, Joshua G.; Prendergast, E.N.; Geddings, Julia E.; Walts, Ann E.; Agadjanian, Hasmik; Hisada, Yohei; Karlan, Beth Y.; Mackman, Nigel; Walsh, Christine

doi:10.1016/j.ygyno.2017.04.021

Cited by 50 publications

(39 citation statements)

References 39 publications

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“…Pancreatic cancer has the highest EV TF activity (16‐ to 26‐fold higher than healthy controls) among different types of cancer . Importantly, increased levels of EV TF activity were associated with venous thromboembolism in patients with pancreatic cancer but not in other types of cancer including brain, colorectal, ovarian, and lung cancer . Interestingly, patients with cirrhosis and acute liver injury have 17‐fold and 38‐fold increased levels of EV TF activity compared with healthy controls, respectively .…”

Section: Discussionmentioning

confidence: 98%

“…13 Importantly, increased levels of EV TF activity were associated with venous thromboembolism in patients with pancreatic cancer but not in other types of cancer including brain, colorectal, ovarian, and lung cancer. 13,16,22,23 Interestingly, patients with cirrhosis and acute liver injury have 17-fold and 38-fold increased levels of EV TF activity compared with healthy controls, respectively. 13 Increased levels of EV TF were detected in patients with endotoxemia (nine-fold) and urinary tract infection (six-fold).…”

Section: Discussionmentioning

confidence: 99%

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Measurement of tissue factor activity in extracellular vesicles from human plasma samples

Hisada

Mackman

2019

Research and Practice in Thrombosis and Haemostasis

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Tissue factor (TF) is the cellular receptor for plasma factor (F) VII/FVIIa and triggers blood coagulation. Extracellular vesicles (EVs) are small membrane vesicles that are released from activated cells and tumor cells. Different cell types, including activated monocytes and tumors cells release TF‐positive EVs into the circulation. We developed an assay to measure levels of TF activity in EVs isolated from human plasma samples. We and others have used this assay to demonstrate increased levels of EV TF activity in a variety of diseases associated with thrombosis, including cancer. These studies suggest that EV TF can be used as a biomarker of thrombotic risk. The strength of this laboratory assay is that it is relatively sensitive and specific. However, the limitations of the assay are that it is labor intensive and the coefficient of variation is too high for it to be used as a clinical assay.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Measurement of tissue factor activity in extracellular vesicles from human plasma samples

Hisada

Mackman

2019

Research and Practice in Thrombosis and Haemostasis

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“…Massive ascites was also likely identified due to hemoconcentration caused by intravascular dehydration, in addition to the direct compression applied to veins by the ascites. Clear cell carcinoma was identified as an independent and significant risk factor, possibly because clear cell carcinoma has significantly higher TF expression compared to other histological types, indicating that the extrinsic coagulation pathway may be accelerated. Additionally, stage III/IV advanced cancer, LN enlargement that suggests metastasis and tumor extension beyond the primary organ were identified as independent and significant risk factors for pretreatment VTE, and this may be a consequence of augmentation in blood coagulation through basement membrane destruction and interstitial infiltration caused by tumor extension/metastasis and stimulation from and the immune response to intravascular/intraductal entry .…”

Section: Discussionmentioning

confidence: 99%

Prevalence of venous thromboembolism at pretreatment screening and associated risk factors in 2086 patients with gynecological cancer

Tasaka

Minaguchi

Hosokawa

et al. 2020

J of Obstet and Gynaecol

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Aim: Postoperative pulmonary embolism can be a fatal surgical complication and is thought to occur secondary to asymptomatic venous thromboembolism (VTE) that exists preoperatively in some patients. The purpose of this study was to clarify the frequency and risk factors of pretreatment VTE in gynecological cancer patients. Methods: This study investigated 2086 patients with gynecological cancer (cervix, n = 754; endometrium, n = 862; ovary, n = 470) who underwent initial treatment between 2004 and 2017. Pretreatment VTE screening was performed with D-dimer (DD) levels in these patients. Based on this, the associated risk factors were retrospectively analyzed. Results: Pretreatment VTE was discovered in 7.3% of patients with cervical cancer, 11.5% of those with endometrial cancer and 27.0% of those with ovarian cancer. Significant independent risk factors were: age greater than or equal to 60 years and tumor long diameter greater than or equal to 40 mm for cervical cancer; age greater than or equal to 60 years, stage III/IV advanced disease, clear cell carcinoma and tumor long diameter greater than or equal to 60 mm for endometrial cancer; and age greater than or equal to 60 years, clear cell carcinoma and massive ascites for ovarian cancer. Conclusion: Pretreatment asymptomatic VTE is very frequent in gynecological cancer patients. It may be beneficial to consider measuring DD or performing venous ultrasonography in patients with the above risk factors.

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“…The function of TF-exposing EVs has been extensively studied in vitro as well as in vivo [15,[37][38][39][40]. Tumorderived TF-exposing EVs induce platelet aggregation [15,41] and enhance the size of venous clots in mice [38].…”

Section: Discussionmentioning

confidence: 99%

Extracellular vesicles from human saliva promote hemostasis by delivering coagulant tissue factor to activated platelets

Gool

Berckmans

et al. 2018

Journal of Thrombosis and Haemostasis

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Background Extracellular vesicles (EVs) from human saliva expose coagulant tissue factor (TF). Whether such TF-exposing EVs contribute to hemostasis, however, is unknown. Recently, in a mice model, tumor cell-derived EVs were shown to deliver coagulant TF to activated platelets at a site of vascular injury via interaction between P-selectin glycoprotein ligand-1 (PSGL-1) and P-selectin. Objectives We hypothesized that salivary EVs may deliver coagulant TF to activated platelets via interaction with P-selectin. Methods We investigated the presence of two ligands of P-selectin on salivary EVs, PSGL-1 and CD24. Results Salivary EVs expose CD24 but PSGL-1 was not detected. Immune depletion of CD24-exposing EVs completely abolished the TF-dependent coagulant activity of cell-free saliva, showing that coagulant TF and CD24 co-localize on salivary EVs. In a whole blood perfusion model, salivary EVs accumulated at the surface of activated platelets and promoted fibrin generation, which was abolished by an inhibitory antibody against human CD24. Conclusions A subset of EVs in human saliva expose coagulant TF and CD24, a ligand of P-selectin, suggesting that such EVs may facilitate hemostasis at a site of skin injury where the wound is licked in a reflex action.

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Evaluation of venous thrombosis and tissue factor in epithelial ovarian cancer

Cited by 50 publications

References 39 publications

Measurement of tissue factor activity in extracellular vesicles from human plasma samples

Measurement of tissue factor activity in extracellular vesicles from human plasma samples

Prevalence of venous thromboembolism at pretreatment screening and associated risk factors in 2086 patients with gynecological cancer

Extracellular vesicles from human saliva promote hemostasis by delivering coagulant tissue factor to activated platelets

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