Tissue factors and venous thromboembolism in cancer patients / 浙江大学学报·医学版

Malignant tumor is one of the important acquired risk factors of venous thromboembolism (VTE). As the transmembrane receptor of coagulation factor Ⅶ and activated coagulation factor Ⅶa

Análise da expressão imuno-histoquímica do fator tecidual no carcinoma gástrico: correlações com prognóstico e sobrevida / Immunohistochemical analysis of tissue factor expression in gastric carcinoma: correlations with prognosis and survival

RESUMO Objetivo: estudar a expressão do fator tecidual (FT) e sua correlação com o prognostico e sobrevida em pacientes com carcinoma gástrico. Métodos: verificamos a expressão imuno-histoquímica do FT em 50 espécimes de adenocarcinomas gástricos de pacientes submetidos a tratamento cirúrgico com intenção curativa. A intensidade da sua expressão foi comparada com dados clínicos e patológicos, estadiamento TNM, fatores prognósticos e sobrevida. Resultados: houve expressão do FT em todos os tumores; a intensidade de expressão do FT não foi associada com estágio TNM, variáveis clínicas ou patológicas ou sobrevida geral. Conclusão: este estudo mostra que o FT tem uma expressão elevada em carcinoma gástrico, mas que este não é útil como marcador de prognóstico.

ABSTRACT Objective: to study the expression of the tissue factor (TF) and its correlation with prognosis and survival in patients with gastric carcinoma. Methods: we measured the immunohistochemical expression of TF in 50 specimens of gastric adenocarcinomas from patients submitted to curative surgery. We then compared the intensity of its expression with clinical and pathological data, TNM staging, prognostic factors and survival. Results: all tumors displayed TF expression; the intensity of TF expression was not associated with TNM stage, clinical or pathological variables or general survival. Conclusion: TF has a high expression in gastric carcinoma, but that it is not useful as a prognostic marker.

The involvement of endothelial mediators in leprosy

Leprosy is a chronic infectious disease that requires better understanding since it continues to be a significant health problem in many parts of the world. Leprosy reactions are acute inflammatory episodes regarded as the central etiology of nerve damage in the disease. The activation of endothelium is a relevant phenomenon to be investigated in leprosy reactions. The present study evaluated the expression of endothelial factors in skin lesions and serum samples of leprosy patients. Immunohistochemical analysis of skin samples and serum measurements of VCAM-1, VEGF, tissue factor and thrombomodulin were performed in 77 leprosy patients and 12 controls. We observed significant increase of VCAM-1 circulating levels in non-reactional leprosy (p = 0.0009). The immunostaining of VEGF and tissue factor was higher in endothelium of non-reactional leprosy (p = 0.02 for both) than healthy controls. Patients with type 1 reaction presented increased thrombomodulin serum levels, compared with non-reactional leprosy (p = 0.02). In type 2 reaction, no significant modifications were observed for the endothelial factors investigated. The anti-inflammatory and antimicrobial activities of the endotfhelial factors may play key-roles in the pathogenesis of leprosy and should be enrolled in studies focusing on alternative targets to improve the management of leprosy and its reactions.

Antiinflamatorios no esteroides: seguridad gastrointestinal, cardiovascular y renal / Nonsteroidal antiinflammatory drugs: gastrointestinal and cardiovascular and renal safety

La selección de un medicamento específico perteneciente a una clase farmacológica es bajo criterios de eficacia, seguridad, costo y conveniencia. Los Antiinflamatorios No Esteroideos (AINEs) actualmente se constituyen en uno de los medicamentos más consumidos en el mundo, por lo tanto es de gran importancia la revisión de los aspectos de seguridad de este grupo farmacológico. El presente trabajo tiene el objetivo de analizar bajo las evidencias disponibles hasta la actualidad, la seguridad de los AINES con 3 criterios principales: gastrolesividad, cardiotoxicidad y nefrotoxicidad.

The choice of a specific medication belonging to a drug class is under the criteria of efficacy, safety, cost and suitability. NSAIDs currently constitute one of the most consumed drugs in the world, so it is very important review of the safety aspects of this drug class. This review has the objective of analyze the safety of NSAIDs on 3 main criteria: gastrolesivity, cardiotoxicity and nephrotoxicity.

Increased Tissue Factor Expression is an Independent Predictor of Mortality in Clear Cell Carcinoma of the Kidney

Purpose Increased expression of tissue factor (TF), a primary initiator of the extrinsic coagulation pathway, has been associated with a worse prognosis in a variety of solid tumors. We report for the first time the correlation of the immunohistochemical expression of tissue factor with clinical and pathological outcomes in clear cell carcinomas of the kidney. Materials and Methods immunohistochemical expression of tissue factor was evaluated in 58 paraffin-embedded samples of clear cell carcinomas of the kidney treated at the same university hospital, that was correlated with clinical and pathological variables and with overall survival. Results high intensity tissue factor expression (TF area > 10µm2) was observed in 22.4% of the tumors (13 patients), and was an important predictor of overall mortality, both in univariate and multivariate analysis (p < 0.05). Median overall survival for both groups was 66 months; 78.2 months for patients in the group of lower TF expression and 27.5 months for patients in the group of higher TF expression (log rank p < 0.001). The hazard ratio for mortality was 9.7 (CI 3.7-25.6) for tumors with increased TF expression. Conclusions Increased immunohistochemical expression of TF was an important independent predictor of mortality in a contemporary cohort of patients with clear cell carcinoma of the kidney. Further studies are necessary to define the role of TF in clinical practice. .

Increased expression of tissue factor and protease-activated receptor-1 does not correlate with thrombosis in human lung adenocarcinoma

A correlation between cancer and hypercoagulability has been described for more than a century. Patients with cancer are at increased risk for thrombotic complications and the clotting initiator protein, tissue factor (TF), is possibly involved in this process. Moreover, TF may promote angiogenesis and tumor growth. In addition to TF, thrombin seems to play a relevant role in tumor biology, mainly through activation of protease-activated receptor-1 (PAR-1). In the present study, we prospectively studied 39 lung adenocarcinoma patients in relation to the tumor expression levels of TF and PAR-1 and their correlation with thrombosis outcome and survival. Immunohistochemical analysis showed TF positivity in 22 patients (56 percent), most of them in advanced stages (III and IV). Expression of PAR-1 was found in 15 patients (39 percent), most of them also in advanced stages (III and IV). Remarkably, no correlation was observed between the expression of TF or PAR-1 and risk for thrombosis development. On the other hand, patients who were positive for TF or PAR-1 tended to have decreased long-term survival. We conclude that immunolocalization of either TF or PAR-1 in lung adenocarcinoma may predict a poor prognosis although lacking correlation with thrombosis outcome.

Procoagulant properties of human MV3 melanoma cells

A correlation between cancer and prothrombotic states has long been described. More recently, a number of studies have focused on the procoagulant mechanisms exhibited by tumor cells. In the present study, we dissected the molecular mechanisms responsible for the procoagulant activity of MV3, a highly aggressive human melanoma cell line. It was observed that tumor cells strongly accelerate plasma coagulation as a result of: i) expression of the blood clotting initiator protein, a tissue factor, as shown by flow cytometry and functional assays (factor Xa formation in the presence of cells and factor VIIa), and ii) direct activation of prothrombin to thrombin by cells, as evidenced by hydrolysis of the synthetic substrate, S-2238, and the natural substrate, fibrinogen. This ability was highly potentiated by the addition of exogenous factor Va, which functions as a co-factor for the enzyme factor Xa. In contrast, prothrombin activation was not observed when cells were previously incubated with DEGR-factor Xa, an inactive derivative of the enzyme. Moreover, a monoclonal antibody against bovine factor Xa reduced the prothrombin-converting activity of tumor cells. In conclusion, the data strongly suggest that MV3 cells recruit factor Xa from the culture medium, triggering an uncommon procoagulant mechanism.

Change in tissue thromboplastin content of brain following trauma.

BACKGROUND: Tissue thromboplastin (TTP) is an integral membrane protein contributing to coagulopathy after trauma of brain, which is a rich source of TTP. AIMS: A study was undertaken to establish the TTP content of various areas of normal brain and estimate the changes in TTP activity of brain in response to varying degrees of trauma. MATERIALS AND METHODS: Samples from different areas of brain of ten cadavers were used as controls and they were compared with contused brain tissue obtained after surgery in 25 head injury (HI) patients of varying severity. RESULTS: In the study group, the TTP activity of the frontal, parietal, and temporal lobes after HI was significantly raised in contrast to that of the control group. The TTP activity was also significantly higher in the severe HI patients than those having moderate HI. The mode of injury and the time lapse after HI had no significant bearing on the TTP activity. Subjects above 40 years of age demonstrated a higher mean TTP activity after HI, though it was not statistically significant. CONCLUSION: The study provides quantitative data on TTP activity of normal brain and highlights the role of TTP in coagulopathy following HI through its increased activity after HI, more so in the severe HI group.

Plasma Levels of Tissue Factor Antigen in Patients with Non-Insulin-Dependent Diabetes Mellitus

Patients with diabetes mellitus (DM) are associated with an increased risk of thrombosis, and are susceptible to a series of complications including nephropathy. It has also been known that plasma tissue factor (TF) antigen levels increase significantly in certain disease states. To investigate the clinical significance of an association with the various complications in patients with type 2 non-insulin-dependent DM (NIDDM), we measured the plasma levels of TF antigen in 63 patients (35 males and 28 females, mean age 60.8 yrs) with NIDDM and in 22 normal subjects (14 males and 8 females, mean age 56.0 yrs). The mean concentrations of TF were higher for patients with NIDDM (253.7 +/- 144.9 pg/ml) than in normal subjects (187.3 +/- 108.7 pg/ml with marginal statistical significance (p= 0.0530). The TF levels were higher for patients with a nephropathy than for patients without a nephropathy (p=0.0402). There was a significant positive correlation between levels of TF and BUN (r=0.84, p < 0.0001) or creatinine (r=0.93, p < 0.0001). However, TF levels were found to be similar for both groups with and without thrombosis, neuropathy, retinopathy, or infection. These results suggest that plasma TF antigen levels may be associated with nephropathy and they may reflect a renal dysfunction in NIDDM.

Levels of plasma fibrinopeptide-A during surgery and the severity of the operation.

There is evidence to suggest that the rise of fibrinopeptide A (FPA) during surgery is influenced by tissue thromboplastin released during tissue damage. To investigate whether FPA correlates with the severity of the damage of the operation, 39 patients were recruited and venous blood samples were taken pre-operatively, during skin incision, during bowel manipulation and post-operatively for the assay of FPA. The operations are grouped as minor (A), moderate (B), major (C) and very major (D). The peak FPA levels occurred during bowel manipulation in every degree of operations, and ranged between 6.0 to 22.2 pmol/ml. There was a tendency that peak FPA values rose according to the severity of the surgery, however only very major operations (D) are significantly higher when compared with minor operations (A) (p < 0.01). There was no good correlation between peak FPA levels and length of skin incision (p = 0.83, r = 0.04) as well as peak FPA levels and duration of operation (p = 0.90, r = 0.03). Significantly higher levels of FPA in very major operation (D) was due to more excessive tissue damage during surgery, while due to relatively minimal tissue injury, size of skin incision correlated poorly with FPA.

Estudio crítico de la actividad tromboplástica del líquido amniótico en diversas semanas gestacionales / Critical study of the tromboplastic activity of the amniotic fluid in different gestational weeks

Se determinó la actividad tromboplástica del LA en setenta y ocho embarazos normales y patológicos por el método de Quick, en una etapa, modificado por Yaffe, para la medida del tiempo de protombina. Se comprobó el aumento de la actividad tromboplástica con el progreso de la gestación, siendo el coeficiente de correlación r = -0,76. No se observaron diferencias entre los valores de actividad tromboplástica entre embarazos normales y patológicos. En tres de cuatro casos de embarazos postérmino, la actividad tromboplástica del LA fue inferior a 45 s. Nuestros resultados corroboraron los enunciados por Yaffe y difieren de los de Phillips y Davidson

El aumento de la actividad tromboplástica del líquido aminiótico como prueba de madurez fetal (test de aceleración de la coagulación / Tromboplastin increased activity of amniotic fluid as fetal maturity test (blood coagulation acceleration test)

Se presentan los resultados del estudio del líquido amniótico de 50 embarazadas hecho con la finalidad de evaluar la actividad tromboplastínica del mismo con miras a encontrar un método rápido, seguro y de bajo costo pero la medición de la madurez fetal. Además del TAC se analizaron otros parámetros: creatinina, peso fetal, aspecto del líquido y semanas de gestación, ésta última calculada retrospectivamente a partir de la edad gestacional del recién nacido determinada mediane el examen neonatal practicado por pediatras del hospital. Se encontró que los valores del TAC descienden a medida que progresa el embarazo, pero los cifras obtenidas en este estudio son mucho más bajas que las dadas por otros autores. La cifra promedio del TAC fue de 77 segundos pero los embarazos de menos de 36 semanas. No observamos buena correlación entre los pesos fetales y los valores de creatinina con el TAC. Consideramos que el aspecto del líquido amniótico continúa siendo una ayuda importante como una prueba más en la estimación de la madurez fetal: en el 77,4% de los casos hubo concordancia entre el TAC el aspecto del líquido