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)

Recent work on the sea urchin endomesoderm gene regulatory network (GRN) offers many opportunities to study the specification and differentiation of each cell type during early development at a mechanistic level. The mesoderm lineages consist of two cell populations, primary and secondary mesenchyme cells (PMCs and SMCs). The micromere-PMC GRN governs the development of the larval skeleton, which is the exclusive fate of PMCs, and SMCs diverge into four lineages, each with its own GRN state. Here we identify a sea urchin ortholog of the Twist transcription factor, and show that it plays an essential role in the PMC GRN and later is involved in SMC formation. Perturbations of Twist either by morpholino knockdown or by overexpression result in defects in progressive phases of PMC development, including specification, ingression/EMT, differentiation and skeletogenesis. Evidence is presented that Twist expression is required for the maintenance of the PMC specification state, and a reciprocal regulation between Alx1 and Twist offers stability for the subsequent processes, such as PMC differentiation and skeletogenesis. These data illustrate the significance of regulatory state maintenance and continuous progression during cell specification, and the dynamics of the sequential events that depend on those earlier regulatory states.
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PMID:Twist is an essential regulator of the skeletogenic gene regulatory network in the sea urchin embryo. 1849 3

Abnormal proliferation of vascular smooth muscle cells (VSMCs) plays an important role in the development of cardiovascular diseases. PMC (2,2,5,7,8-pentamethyl-6-hydroxychromane) is the most potent hydrophilic derivative of vitamin E. In this study, we investigated the mechanisms of PMC inhibition of VSMC proliferation in vitro and in vivo. PMC (20 and 50 microM) obviously suppressed proliferation of PDGF-BB-stimulated cells, but not resting cells, and arrested cell cycle progression at the G(2)/M phase. A significant reduction in neointimal formation in carotid arteries was observed in PMC (5mg/kg/day)-treated rats after balloon angioplasty. Activation of STAT3, JAK2, PLCgamma1, PKCdelta, and ROS, but not ERK1/2, AKT, or PKCalpha, was markedly inhibited by PMC in PDGF-BB-stimulated VSMCs. Deferoxamine and PMC significantly inhibited the phosphorylation of PLCgamma1 and JAK2 and arrested cell cycle progression at the G(2)/M phase. These events, however, were reversed in the presence of Fe(2+). Moreover, PMC directly inhibited hydroxyl radical formation in both the Fenton reaction and VSMCs according to an electron spin resonance study. In conclusion, this study demonstrates for the first time that PMC inhibits VSMC proliferation in vitro and balloon injury-induced neointimal formation in vivo. The inhibitory mechanism of PMC may involved the inhibition of hydroxyl radical-mediated PLCgamma1-PKCdelta and JAK2-STAT3 activation and causes cell cycle arrest at the G(2)/M phase. PMC treatment may represent a novel approach for lowering the risk of or improving function in abnormal VSMC proliferation-related vascular diseases.
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PMID:Inhibition of vascular smooth muscle cell proliferation by the vitamin E derivative pentamethylhydroxychromane in an in vitro and in vivo study: pivotal role of hydroxyl radical-mediated PLCgamma1 and JAK2 phosphorylation. 2060 Aug 39

Chronic Myeloid Leukaemia (CML) shows an excellent response to allogeneic bone marrow transplantation (BMT) with a 60-80% long term disease free survival in recipients of unmanipulate marrow. The most frequent cause of treatment failure is leukaemic relapse, due to the re-emergence of malignant recipient clones. Clinical and haematological relapse is usually preceded by molecular evidence of relapse. Early detection of molecular relapse may allow intervention with immunotherapy such as donor lymphocyte infusions (DLI). This study was undertaken to compare results from two centres who employ either Fluorescent In Situ Hybridisation (FISH) or polymerase chain reaction (PCR) analysis of DNA polymorphisms as their routine method of detecting residual host cells following BMT for CML in order to establish (1) if these methods are equivalent for routine laboratory use in reporting of chimaerism results to the referring clinician, and (2) if these methods are beneficial for indicating new and early therapeutic strategies. FISH analyses for the X and Y chromosomes (in sex mismatched patients) and/or FISH for BCR and ABL loci were compared with short tandem repeat PCR (STR-PCR) and conventional karyotyping in serial analyses in 25 patients submitted to BMT for Philadelphia positive (Ph) CML. Comparison of all results on samples assessed between 1 and 13 years post BMT indicated that FISH and PCR, performed on the same bone marrow samples displayed similar results in more than 90% of patients in first 3 years after BMT which increased to a concordance rate of 100% in long term survivors. In contrast, comparison of FISH or PCR versus cytogenetic analysis indicated a low concordance rate, with less than 50% of samples showing similar results during all the follow-up period. Eighty percent of recipients (22 patients) had evidence of mixed chimaerism following BMT (initial level of positivity 1-6% recipient cells) during the follow-up period. This low percentage of recipient cells remained stable in 7 patients, while 9 patients reverted to a donor profile. All 16 patients are in haematological remission. In addition the 3 patients with complete donor chimaerism remain in remission. In the remaining 6 patients, a progressive increase in recipient cells occurred (progressive mixed chimaerism, PMC), and was followed by haematological relapse. We conclude that FISH and PCR can be used to monitor CML patients post BMT and transient or stable low level mixed chimaerism is not associated with leukaemia relapse, but PMC is predictive of imminent relapse and its detection may help to illucidate the timing of early intervention with donor lymphocyte infusion.
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PMID:Comparative Study of FISH, PCR and Cytogenetics on 25 Patients Submitted to Bone Marrow Transplantation (BMT) for Chronic Myelogenous Leukemia (CML); Which Tests can we Use in Routine Analysis Post BMT? 2741 28