Haemostatic Changes; Plasma Levels of Alpha2-Antiplasmin-Plasmin Complex and Thrombin-Antithrombin III Complex in Female Breast Cancer

Özyılkan, Özgür; Baltali, E; Özdemir, Oktay; Tekuzman, Gülten; Kirazlı, Şerafettin; Firat, D.

doi:10.1177/030089169808400310

Cited by 22 publications

(16 citation statements)

References 20 publications

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“…Because the cAT content in the plasma declined after tumor excision surgery and was generally associated with PADI4 levels in the blood, we propose that the high cAT levels observed in the blood was due to citrullination of PADI4 in tumor tissues. Suppressed antithrombin III activity and unregulated thrombin activity have broadly been reported in the plasma of patients with lung adenocarcinomas, renal cell carcinomas, breast cancer, malignant melanomas, colon cancer, pancreatic adenocarcinomas, and larynx squamous cell carcinomas [13-16]. Thrombin activity can promote angiogenesis by increasing transcription of the VEGF receptor as well as metastasis and hyperplasia by inducing expression of integrin β 3 [17-19].…”

Section: Discussionmentioning

confidence: 99%

Increased PADI4 expression in blood and tissues of patients with malignant tumors

et al. 2009

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BackgroundPeptidylarginine deiminase type 4 (PAD4/PADI4) post-translationally converts peptidylarginine to citrulline. Recent studies suggest that PADI4 represses expression of p53-regulated genes via citrullination of histones at gene promoters.MethodsExpression of PADI4 was investigated in various tumors and non-tumor tissues (n = 1673) as well as in A549, SKOV3 and U937 tumor cell lines by immunohistochemistry, real-time PCR, and western blot. Levels of PADI4 and citrullinated antithrombin (cAT) were investigated in the blood of patients with various tumors by ELISA (n = 1121).ResultsImmunohistochemistry detected significant PADI4 expression in various malignancies including breast carcinomas, lung adenocarcinomas, hepatocellular carcinomas, esophageal squamous cancer cells, colorectal adenocarcinomas, renal cancer cells, ovarian adenocarcinomas, endometrial carcinomas, uterine adenocarcinomas, bladder carcinomas, chondromas, as well as other metastatic carcinomas. However, PADI4 expression was not observed in benign leiomyomas of stomach, uterine myomas, endometrial hyperplasias, cervical polyps, teratomas, hydatidiform moles, trophoblastic cell hyperplasias, hyroid adenomas, hemangiomas, lymph hyperplasias, schwannomas, neurofibromas, lipomas, and cavernous hemangiomas of the liver. Additionally, PADI4 expression was not detected in non-tumor tissues including cholecystitis, cervicitis and synovitis of osteoarthritis, except in certain acutely inflamed tissues such as in gastritis and appendicitis. Quantitative PCR and western blot analysis showed higher PADI4 expression in gastric adenocarcinomas, lung adenocarcinomas, hepatocellular carcinomas, esophageal squamous cell cancers and breast cancers (n = 5 for each disease) than in the surrounding healthy tissues. Furthermore, western blot analysis detected PADI4 expression in cultured tumor cell lines. ELISA detected increased PADI4 and cAT levels in the blood of patients with various malignant tumors compared to those in patients with chronic inflammation and benign tumors. This was consistent with immunohistochemical results. Additionally, PADI4 and cAT levels were significantly associated with higher levels of known tumor markers.ConclusionOur results suggest that PADI4 expression is increased in the blood and tissues of many malignant tumors, a finding useful for further understanding of tumorigenesis.

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Section: Discussionmentioning

confidence: 99%

Increased PADI4 expression in blood and tissues of patients with malignant tumors

et al. 2009

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“…Previous work has demonstrated a hypercoagulable state in breast cancer patients, with elevated markers of coagulation, including thrombin -antithrombin (TAT) (Falanga et al, 1998;Ozyilkan et al, 1998), fibrinogen (Miller and Heilmann, 1988), D-dimer (Blackwell et al, 2000;Oberhoff et al, 2000) and tissue factor (TF) (Lwaleed et al, 1999;Ueno et al, 2000).…”

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confidence: 99%

Early changes in the haemostatic and procoagulant systems after chemotherapy for breast cancer

et al. 2008

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Venous thromboembolism (VTE) following breast cancer chemotherapy is common. Chemotherapy-induced alterations in markers of haemostasis occur during chemotherapy. It is unclear how rapidly this occurs, whether this is upregulated in patients developing VTE and whether changes predict for VTE. Markers of haemostasis, functional clotting assays and vascular endothelial growth factor were measured before chemotherapy and at 24 h, 4 days, 8 days and 3 months following commencement of chemotherapy in early and advanced breast cancer patients and in age-and sex-matched controls. Duplex ultrasound imaging was performed after 1 month or if symptomatic. Of 123 patients, 9.8% developed VTE within 3 months. Activated partial thromboplastin time (APTT), prothrombin time (PT), D-dimer, fibrinogen, platelet count, VEGF and fibrinogen were increased in cancer. Fibrinogen, D-dimer, VEGF and tissue factor were increased, at baseline, in patients subsequently developing VTE. D-dimer of less than 500 ng ml À1 has a negative predictive value of 97%. Activated partial thromboplastin time, PT and thrombin -antithrombin showed significantly different trends, as early as within 24 h, in response to chemotherapy in patients subsequently developing VTE. Markers of coagulation and procoagulants are increased, before chemotherapy, in patients who subsequently develop VTE. A group of patients at minimal risk of VTE can be identified, allowing targeted thrombopropylaxis to the higher risk group.

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“…Increased TAT levels show coagulation activation [22]. Ozyilkan et al determined a similar escalation in patients with breast cancer [23]. Seitz et al observed increased TAT levels in patients with lung cancer [10].…”

Section: Discussionmentioning

confidence: 99%

The effect of adjuvant chemotherapy on plasma TAT and F 1+2 levels in patients with breast cancer

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Kavgacı

Canyılmaz

et al. 2015

Biomedicine & Pharmacotherapy

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Haemostatic Changes; Plasma Levels of Alpha2-Antiplasmin-Plasmin Complex and Thrombin-Antithrombin III Complex in Female Breast Cancer

Abstract: We demonstrated that increased APP and TAT levels might reflect enhanced activation of coagulation and the fibrinolytic system in patients with active breast cancer.

Cited by 22 publications

References 20 publications

Increased PADI4 expression in blood and tissues of patients with malignant tumors

Increased PADI4 expression in blood and tissues of patients with malignant tumors

Early changes in the haemostatic and procoagulant systems after chemotherapy for breast cancer

The effect of adjuvant chemotherapy on plasma TAT and F 1+2 levels in patients with breast cancer

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