Mouse anti-CFL1 Monoclonal antibody, clone MAFB3953

Glioblastoma multiforme (GBM) is the most common and the most aggressive primary malignant tumor of the brain. Prognostic factors in GBM can be sorted as age, tumor localization, tumor diameter, symptom period and type, the extent of surgery, postoperative tumor volume, and adjuvant radiotherapy and/or chemotherapy status. Besides the interactions between actin microfilaments, microtubules, and intermediate filaments, environmental factors and intracellular signals which regulate them affect the cell invasion. Rho proteins and therefore Rho-kinase activation play important role at these changes. The aim of this study is to evaluate the relationship between the Rho-kinase pathway gene expressions and prognosis in GBM. Ninety-eight patients diagnosed as GBM between 2001 and 2010 were enrolled into the study. RNA was obtained from the paraffinized tumor tissue of the patients with formalin-fixed, paraffin-embedded RNA isolation kit and the mRNA expressions of 26 genes were investigated. There was a statistically significant negative correlation between the ages at the diagnosis and survival. There was a significant relationship between the overexpression of Rho-kinase pathway-related genes LIMK1, CFL1, CFL2, and BCL2 and low expression of MAPK1 gene and the survival of the patients. These results demonstrate for the first time that there is a marked contribution of Rho-kinase pathway-related genes to the progression and survival of the GBM. The expression of these genes may be related to response of multimodal therapy or these parameters could be used to determine possible unresponsive patients before treatment.

Genetic factors underlying the human limb abnormality congenital talipes equinovarus ('clubfoot') remain incompletely understood. The spontaneous autosomal recessive mouse 'peroneal muscular atrophy' mutant (PMA) is a faithful morphological model of human clubfoot. In PMA mice, the dorsal (peroneal) branches of the sciatic nerves are absent. In this study, the primary developmental defect was identified as a reduced growth of sciatic nerve lateral motor column (LMC) neurons leading to failure to project to dorsal (peroneal) lower limb muscle blocks. The pma mutation was mapped and a candidate gene encoding LIM-domain kinase 1 (Limk1) identified, which is upregulated in mutant lateral LMC motor neurons. Genetic and molecular analyses showed that the mutation acts in the EphA4-Limk1-Cfl1/cofilin-actin pathway to modulate growth cone extension/collapse. In the chicken, both experimental upregulation of Limk1 by electroporation and pharmacological inhibition of actin turnover led to defects in hindlimb spinal motor neuron growth and pathfinding, and mimicked the clubfoot phenotype. The data support a neuromuscular aetiology for clubfoot and provide a mechanistic framework to understand clubfoot in humans.