JAK2 mutation status, hemostatic risk factors and thrombophilic factors in essential thrombocythemia (ET) patients

The recently discovered JAK2 V617F point mutation, found in 50–60% of ET patients, has been reported to be associated with a higher risk of thrombotic events. In this study, we explored if JAK2 V617F mutation, or coexisting thrombophilic and hemostatic risk factors, contributed to these complications. We examined 32 patients with ET, and looked for pathogenetic JAK2 V617F mutation and prothrombotic genes mutations: factor V Leiden, prothrombin and MTHFR. We also evaluated plasma levels of fibrinogen, factors VIII and XII, AT, protein C, protein S and serum level of homocysteine. Urokinase concentration was assessed in patients’ plasma as well as platelet lysates. There was no difference in the number of thrombotic complications between ET patients with and without JAK2 mutation. However, we found a number of thrombophilic and hemostatic risk factors that could contribute to thrombotic complications in ET patients. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 2, pp. 267–271

Mild hyperhomocysteinemia in patients with essential thrombocythemia (ET) and its relation with MTHFR gene mutation and folic acid concentration

In this study we assessed homocysteine level in 106 patients with ET – 80 females and 26 males, mean age 54 (23–82) and in 20 healthy persons – 6 males and 14 females, mean age 41 (31–54). We also searched for a relation between homocysteine level and MTHFR gene mutation as well as vitamin B12 and folic acid concentration. Median homocysteine serum level was higher in ET patients than in control group. Elevated homocysteine level primarily stems from folic acid deficiency rather than from the presence of MTHFR gene mutation. Median folic acid level was lower in ET patients presenting thrombotic and bleeding complications than in ET patient without vascular episodes. We concluded that folic acid substitution may not only prevent hyperhomocysteinemia but also the development of vascular complications in ET patients

Nitric Oxide (NO) and Cyclooxygenase-2 (COX-2) Cross-Talk in Co-Cultures of Tumor Spheroids with Normal Cells

Cyclooxygenases (COX), prostaglandin E2 (PGE2) and nitric oxide (NO) are believed to be some of the most important factors related to colon cancer growth and metastasis. In this study, we aimed to investigate the associations between COX-2, PGE2 and NO in co-cultures of human colon cancer spheroids obtained from different tumor grades with normal human colonic epithelium and myofibroblast monolayers. L-arginine (2 mM), a substrate for nitric oxide synthases (NOS), decreased COX-2 and PGE2 levels, while NG-nitro-L-arginine methyl ester (L-NAME) (2 mM), a NOS inhibitor, had no influence on COX-2 and PGE2 levels but limited tumor cell motility. NS398 (75 μM), a selective COX-2 inhibitor, had no significant influence on NO level but decreased motility of tumor cells. COX-2, PGE2 and NO levels depended on the tumor grade of the cells, being the highest in Duke’s stage III colon carcinoma. Summing up, we showed that addition of L-arginine at doses which did not stimulate NO level caused a significant decrease in COX-2 and PGE2 amounts in co-cultures of colon tumor spheroids with normal epithelial cells and myofibroblasts. Any imbalances in NO level caused by exogenous factors influence COX-2 and PGE2 amounts depending on the kind of cells, their reciprocal interactions and the local microenvironmental conditions. The knowledge of these effects may be useful in limiting colon carcinoma progression and invasion