Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The registry of patients treated with Thromboreductine (anagrelid) in the contributing centres in the Czech Republic has been updated with data on the patients receiving this medication since 2004. The original purpose of the registry was to record responses to Thromboreductine therapy and adverse drug reactions in patients with essential thrombocytopenia. However, data on additional Ph negative myeloproliferations, as well as data on cytoreductive therapies other than exclusively that using Thromboreductine has also been recorded in the course of its compilation, including data on combined regimes. At present, the database contains data on 421 patients, and valid conclusions can be drawn if the level of data filling is enhanced. Evaluation has been currently focused on the analysis of the risk of development of clinical symptoms of thrombosis and on the standards of treatment from the viewpoint of the achieved treatment response. Analyses of data from the registry corroborate the special importance of the proof of JAK2 mutation, and of the test for factor V Leiden mutation, and of protein of S for the assessment of the risk of thromboembolic complications. The output of the analysis confirms that anagrelid is a very efficient thromboreductive agent the administration of which is associated with a low incidence of non-serious adverse effects (10.9%). However, in spite of a fast response to therapy, the therapeutic goal consisting in the reduction of the platelet count below 400 (or below 600) x 10(9)/l, i.e. the complete (or partial) treatment response, is relatively slow to achieve. This is likely to be due to lack of radical corrections in the dosage of the drug for different reasons.
 ...
PMID:[What is the current treatment of patients with essential thrombocytopenia and other myeloproliferations accompanied with thrombocythemia [corrected] and what can be the predictive sign of the risk of thrombosis in such patients--a report from the registry of patients treated by Thromboreductine]. 1878 May 77

The Philadelphia negative myeloproliferative neoplasms include polycythaemia vera (PV), essential thrombocytopenia (ET) and primary myelofibrosis (PMF). Patients with these conditions were mainly thought to harbour JAK2V617F mutations or an Myeloproliferative leukaemia (MPL) substitution. In 2013, two revolutionary studies identified recurrent mutations in a gene that encodes the protein calreticulin (CALR). This mutation was detected in patients with PMF and ET with non-mutated JAK2 or MPL but was absent in patients with PV. The CALR gene encodes the calreticulin protein, which is a multifactorial protein, mainly located in the endoplasmic reticulum in chromosome 19 and regulates calcium homeostasis, chaperones and has also been implicated in multiple cellular processes including cell signalling, regulation of gene expression, cell adhesion, autoimmunity and apoptosis. Somatic 52 bp deletions and recurrent 52 bp insertion mutations in CALR were detected and all resulted in frameshift and clusters in exon 9 of the gene. This review will summarise the current knowledge on the CALR gene and mutation of the gene in pathological conditions and patient phenotypes.
...
PMID:The Calreticulin gene and myeloproliferative neoplasms. 2735 6

For the first time, NCCN has published guidelines specifically geared toward treating myeloproliferative neoplasms (MPNs). The first set of guidelines was developed for myelofibrosis (MF), and was presented at the NCCN 22nd Annual Conference. Future guidelines will be issued for polycythemia vera, essential thrombocytopenia, and atypical MPNs. Patients with MF can have an unpredictable course, one that is largely dependent on the presence of certain molecular alterations. Models are currently emerging that take into account molecular factors. Only one drug is currently approved for MF, the oral JAK1/2 inhibitor ruxolitinib, which has been shown to significantly reduce splenomegaly and improve symptoms.
 ...
PMID:NCCN Debuts New Guidelines for Myeloproliferative Neoplasms. 2851 54

Thrombosis has been recognized as one of the most significant risk factors of high mortality and disability in patients with Philadelphia (Ph) chromosome negative myeloproliferative neoplasms (MPNs). However, the risk factors of thrombotic events in these patients have not been completely understood. In this study, the clinical data of 58 patients with Ph-MPNs were obtained and analyzed, including 34 cases of essential thrombocytopenia (ET), 23 thrombotic events happened in 21 (36%) patients, among which 60% (14 of 23) with cerebral infarction, 17% (4 of 23) with coronary heart disease and 23% (5 of 23) with venous thrombosis. There were no significant differences in age, sex, and blood cell count between polycythemia vera (PV) and ET patients who have experienced thrombotic events and those who have not. In ET patients, the incidence of thrombotic events in plasminogen activator inhibitor-1 (PAI-1) genotype 4G4G was significantly higher than that in genotype 4G5G and genotype 5G5G (P < .05). The incidence of thrombotic events in PV and ET patients with infection was higher than those without infection (P < .05). Using logistic regression analysis, we found that PAI-1 genotype 4G4G and infection were associated with thrombotic events (odds ratio 6.744, 95% CI: 1.195-38.056 and 15.641 95% CI: 3.327-73.522). The 4G/4G polymorphism of PAI-1 gene and infection are independent risk factors of thrombotic events in patients with Ph-MPNs. PAI-1 gene 4G4G and infection in ET and PV patients with Janus kinase 2 (JAK2) V617F mutation were shown to be high risk of thrombotic events. Therefore, clinical doctors should put more attention on PAI-1 genotype 4G4G and infection in JAK2 V617F mutated patients with Ph-MPNs to prevent the thrombosis.
 ...
PMID:Correlation Between PAI-1 Gene 4G/5G Polymorphism and the Risk of Thrombosis in Ph Chromosome-Negative Myeloproliferative Neoplasms. 3268 89