thromboplastin and Uterine-Neoplasms

The paper reviews the current studies on mechanism of thrombo-embolic complications in patients with malignancy. The neoplastic cells can express procoagulants like tissue factor (TF), cancer procoagulant (CP) and others, which induce thrombin formation in blood plasma and cause thrombo-embolic events, disseminated intravascular coagulation and other complications. Both procoagulants are acting via extrinsic pathway--TF makes complexes with factor VII and calcium ions, while CP acts directly on factor X transforming it into active form (Xa). Gynecological tumor-related complications occur in 20-30% patients with ovarian or uterine cancer.

Topics: Antineoplastic Agents; Female; Humans; Neoplasms; Ovarian Neoplasms; Thromboembolism; Thromboplastin; Uterine Neoplasms

miR-93/106b and their host gene minichromosome maintenance complex component 7 (MCM7) reside at chr7q22, a region frequently rearranged in leiomyomas. We explored the expression of miR-93/106b in leiomyoma and paired myometrium (n = 63) from untreated and patients exposed to hormonal therapies (GnRH agonist, Depo-Provera, and oral contraceptives) from African-Americans and Caucasians and their regulatory functions in isolated paired (n = 15) leiomyoma and myometrial smooth muscle cells and the leiomyosarcoma cell line. At tissue level leiomyomas expressed significantly lower levels of miR-93 and elevated MCM7 as compared with myometrium with limited racial influence or hormonal exposure on their expression. Assessing the regulatory function of miR-93/106b through doxycycline-inducible lentiviral transduction in a microarray analysis, tissue factor (F3) and IL8 were identified as their possible targets. At the tissue level, leiomyomas expressed a significantly lower level of F3 and an elevated IL-8 level, which exhibited an inverse relationship with miR-93 but with limited racial or hormonal influences. The gain of function of miR-93/106b in leiomyoma smooth muscle cells, myometrial smooth muscle cells, and the leiomyosarcoma cell line dose dependently repressed F3 and IL8 through direct interactions with their respective 3'-untranslated region and indirectly through F3 repression inhibited IL8, CTGF, and PAI-1 expression, confirmed by using small interfering RNA silencing or factor Vlla (FVIIa) activation of F3, as well as reducing the rate of proliferation, while increasing caspase-3/7 activity. We concluded that differential expression of miR-93/106b and their direct and/or indirect regulatory functions on F3, IL8, CTGF, and PAI-1 expression, with key roles in inflammation and tissue turnover may be of significance in the outcome of leiomyoma growth and associated symptoms.

Topics: Adult; Caspases; Cell Cycle Proteins; Cell Proliferation; Cell Survival; Cells, Cultured; Cluster Analysis; DNA-Binding Proteins; Female; Gene Expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Interleukin-8; Leiomyoma; Menstrual Cycle; MicroRNAs; Middle Aged; Minichromosome Maintenance Complex Component 7; Myometrium; Nuclear Proteins; RNA Interference; Thromboplastin; Uterine Neoplasms; Young Adult

During pregnancy, important modifications of hemostasis occur resulting in mothers in hypercoagulability and the role of placental cells such as trophoblast cells has been hypothesized. In this study, we first showed that syncytiotrophoblast plasma membranes, isolated from normal human placenta, expressed a strong tissue factor (TF) activity. We then studied TF activity of two continuous trophoblast cell lines (JEG-3 and BeWo) in comparison to human umbilical vein endothelial cells (HUVEC) and transformed human endothelial cells (ECV-304). TF assays were performed on intact detached confluent cells. Unstimulated JEG-3 and BeWo cells exhibited a very high TF activity which slightly increased after 2 to 4 h TNF-alpha stimulation. In contrast, HUVEC and ECV-304 had a lower basal TF activity which was mainly inducible by TNF-alpha, with a maximum effect after 4 to 6 h stimulation. For both cell types, TF activity was decreased to basal value after 16-hour TNF-alpha stimulation. These results support that trophoblast cells are able to express TF but the involvement of this property in the hemostatic physiological changes observed during pregnancy, remains to be demonstrated.

Topics: Cell Line, Transformed; Cell Membrane; Cells, Cultured; Choriocarcinoma; Cycloheximide; Dactinomycin; Endothelium, Vascular; Female; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Humans; Neoplasm Proteins; Pregnancy; Thromboplastin; Trophoblasts; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha; Umbilical Veins; Uterine Neoplasms

High-sensitivity thromboplastin reagents suitable for use in the prothrombin time (PT) assay are typically prepared from human brain and placenta, tissues that are in limited supply and subject to viral contamination. Cloning and expression of recombinant human tissue factor (TF) has enabled production of a new generation of thromboplastin reagents whose performance and utility are under active investigation. The purpose of this study was to determine the feasibility of producing a sensitive human thromboplastin reagent from a non-recombinant source: cultured human cells. Several human cell lines with apparently high constitutive TF synthesis were identified, and a viable thromboplastin reagent (Humaplastin) was produced from a human lung cell line via a non-conventional process that did not require reconstitution or rehydration of TF in cell membranes. When calibrated against BCT/253, a human brain international reference thromboplastin, Humaplastin exhibited a mean normal prothrombin time of 12.6 +/- 0.7 s (mean +/- SD: n = 20) and an International Sensitivity Index of 1.09 +/- 0.019. The performance of this reagent was well correlated (r = 0.983) with Thromborel S, a commercially available human placental thromboplastin reagent. Orthogonal least squares regression of the log PT values from the placental thromboplastin reagent versus Humaplastin and two recombinant TF-based thromboplastin reagents suggested that the latter three reagents are somewhat more sensitive than the placental thromboplastin reagent, although such differences should not be expected to have a significant impact on clinical utility. It is concluded that cultured human lung cells represent a suitable source of tissue thromboplastin for production of a high-sensitivity non-recombinant thromboplastin reagent.

Topics: Adenocarcinoma; Anticoagulants; Astrocytoma; Blood Coagulation Factors; Brain; Brain Neoplasms; Calibration; Carcinoma, Squamous Cell; Cells, Cultured; Choriocarcinoma; Feasibility Studies; Female; Glioblastoma; Histiocytosis, Langerhans-Cell; Humans; Indicators and Reagents; Lung; Lung Neoplasms; Neoplasm Proteins; Placenta; Prothrombin Time; Recombinant Proteins; Reference Standards; Sensitivity and Specificity; Thromboplastin; Tumor Cells, Cultured; Uterine Neoplasms

We found similar levels of thromboplastic activity in molar tissue, vesicular fluid and normal placental tissue from pregnancies matched for gestational age. The fibrinolytic activity of molar tissue and vesicular fluid was, however, increased and vaginal haemorrhage tended to be heavier when fibrinolytic activity was high (p = 0.06). Subsequent choriocarcinoma occurred more frequently in patients with molar tissue which had low fibrinolytic activity (p = 0.08).

Topics: Body Fluids; Female; Fibrinolysis; Humans; Hydatidiform Mole; Hydatidiform Mole, Invasive; Placenta; Pregnancy; Thromboplastin; Tyrosine; Uterine Neoplasms

Topics: Abortion, Induced; Adenocarcinoma; Blood Coagulation Disorders; Carcinoma in Situ; Carcinoma, Squamous Cell; Curettage; Dilatation; Embryo, Mammalian; Female; Fetus; Gestational Age; Humans; Hypernatremia; Hypertonic Solutions; Lymphatic Metastasis; Oxytocin; Pregnancy; Prognosis; Thromboplastin; United States; Uterine Cervical Neoplasms; Uterine Neoplasms; Vaginal Smears