Solomon R.E.,Alliant International University |
Boone K.B.,Alliant International University |
Miora D.,Alliant International University |
Skidmore S.,Alliant International University |
And 4 more authors.
Clinical Neuropsychologist | Year: 2010
In the present study a large sample of credible patients (n = 172) scored significantly higher than a large sample of noncredible participants (n = 195) on several WAIS-III Picture Completion variables: Age Adjusted Scaled Score, raw score, a Rarely Missed index (the nine items least often missed by credible participants), a Rarely Correct index (nine items correct <26% of the time in noncredible participants and with at least a 25 percentage-point lower endorsement rate as compared to credible participants), and a Most Discrepant index (the six items that were the most discrepant in correct endorsement between groupsat least a 40 percentage point difference). Comparison of the various scores showed that the Most Discrepant index outperformed all the others in identifying response bias (nearly 65% sensitivity at 92.8% specificity as compared to at most 59% sensitivity for the other scores). While no differences in Picture Completion scores were observed between less-educated (<12 years) and better-educated (≥12 years) credible participants, noncredible participants with <12 years of education scored significantly poorer than noncredible participants with 12 or more years of education. On the Most Discrepant index, 76.7% of less-educated noncredible participants were detected as compared to 58.3% of better-educated noncredible participants. Results of the current study suggest that the Picture Completion subtest of the WAIS-III is an effective measure of response bias, and that it may have a unique role in identifying suboptimal effort in less-educated test takers. © 2010 Psychology Press. Source
Boone K.B.,Alliant International University |
Lo T.T.Y.,City of Hope Medical Center |
Goldberg H.E.,View Medical |
Cottingham M.E.,Private Practice |
And 3 more authors.
Clinical Neuropsychologist | Year: 2013
Practice guidelines recommend the use of multiple performance validity tests (PVTs) to detect noncredible performance during neuropsychological evaluations, and PVTs embedded in standard cognitive tests achieve this goal most efficiently. The present study examined the utility of the Comalli version of the Stroop Test as a measure of response bias in a large sample of "real world" noncredible patients (n = 129) as compared with credible neuropsychology clinic patients (n=233). The credible group performed significantly better than the noncredible group on all trials, but particularly on word-reading (Stroop A) and color-naming (Stroop B); cut-scores for Stroop A and Stroop B trials were associated with moderate sensitivity (49-53%) as compared to the low sensitivity found for the color interference trial (29%). Some types of diagnoses (including learning disability, severe traumatic brain injury, psychosis, and depression), very advanced age (≥80), and lowered IQ were associated with increased rates of false positive identifications, suggesting the need for some adjustments to cut-offs in these subgroups. Despite some previous reports of an inverted Stroop effect (i.e., color-naming worse than color interference) in noncredible subjects, individual Stroop word reading and color naming trials were much more effective in identifying response bias. © 2013 Taylor & Francis. Source
Pezeshkpour G.H.,West Los Angeles VA |
Moatamed F.,West Los Angeles VA |
Lewis M.,West Los Angeles VA |
Hoang B.,West Los Angeles VA |
And 6 more authors.
Genes and Cancer | Year: 2013
CRK (c-Crk) as an adaptor protein is involved in several oncogenic signal transduction pathways, conveying oncogenic signals to its downstream effectors and thereby affecting multiple cellular processes including proliferation, differentiation, and migration. For example, we have observed that CRK expression and phosphorylation influence the invasiveness of non-small cell lung cancer (NSCLC) cells. To intervene in CRK signaling pathway, we examined whether CRK protein domains can be used as therapeutic tools to interrupt CRK signaling, thus influencing the biological behavior of NSCLC cells. For this purpose, Src Homology domains of CRK-I (i.e., SH2 and SH3N domains) were overexpressed in H157, Rh2, and A549 cells. CRK-SH3N domain expression induced epithelial morphology in H157 cells and enhanced epithelial morphology of A549 and Rh2 cells as compared to cells transfected with CRK-SH2 domain or empty vector. In addition, CRK-SH3N domain expression significantly decreased the motility and invasiveness of A549 and H157 cells. Furthermore, CRK-SH3N domain expression disrupted the interaction of CRK-II with DOCK180. In summary, these data provide evidence that the CRK-SH3N domain can be used to influence the malignant phenotype of NSCLC cells and also reduce the metastatic potential of these cells. © The Author(s) 2013. Source
Mortazavi F.,West Los Angeles VA |
Mortazavi F.,University of California at Los Angeles |
Mortazavi F.,Jonsson Comprehensive Cancer Center |
Lu J.,University of California at Los Angeles |
And 7 more authors.
BMC Cancer | Year: 2015
Background: Key effector(s) of mutated KRAS in lung cancer progression and metastasis are unknown. Here we investigated the role of PAK1/Crk axis in transduction of the oncogenic KRAS signal in non-small cell lung cancer (NSCLC). Methods: We used NSCLC clinical specimens to examine the correlation among KRAS mutations (codon 12, 13 and 61); PAK1/Crk axis activation [p-PAK1(Thr423), p-Crk(Ser41)]; and adhesion molecules expression by immunohistochemistry. For assessing the role of proto-oncogene c-Crk as a KRAS effector, we inhibited KRAS in NSCLC cells by a combination of farnesyltransferase inhibitor (FTI) and geranylgeranyltransferase inhibitor (GGTI) and measured p-Crk-II(Ser41) by western blotting. Finally, we disrupted the signaling network downstream of KRAS by blocking KRAS/PAK1/Crk axis with PAK1 inhibitors (i.e., IPA-3, FRAX597 or FRAX1036) along with partial inhibition of all other KRAS effectors by prenylation inhibitors (FTI + GGTI) and examined the motility, morphology and proliferation of the NSCLC cells. Results: Immunohistochemical analysis demonstrated an inverse correlation between PAK1/Crk phosphorylation and E-cadherin/p120-catenin expression. Furthermore, KRAS mutant tumors expressed higher p-PAK1(Thr423) compared to KRAS wild type. KRAS prenylation inhibition by (FTI + GGTI) completely dephosphorylated proto-oncogene c-Crk on Serine 41 while Crk phosphorylation did not change by individual prenylation inhibitors or diluent. Combination of PAK1 inhibition and partial inhibition of all other KRAS effectors by (FTI + GGTI) dramatically altered morphology, motility and proliferation of H157 and A549 cells. Conclusions: Our data provide evidence that proto-oncogene c-Crk is operative downstream of KRAS in NSCLC. Previously we demonstrated that Crk receives oncogenic signals from PAK1. These data in conjunction with the work of others that have specified the role of PAK1 in transduction of KRAS signal bring forward the importance of KRAS/PAK1/Crk axis as a prominent pathway in the oncogenesis of KRAS mutant lung cancer. © 2015 Mortazavi et al. Source
Rettig M.,West Los Angeles VA |
Rettig M.,University of California at Los Angeles |
Rettig M.,Jonsson Comprehensive Cancer Center |
Trinidad K.,West Los Angeles VA |
And 9 more authors.
PLoS ONE | Year: 2012
The role of c-Crk (CRK) in promoting metastasis is well described however the role of CRK phosphorylation and the corresponding signaling events are not well explained. We have observed CRK-II serine 41 phosphorylation is inversely correlated with p120-catenin and E-cadherin expressions in non-small cell lung cancer (NSCLC) cells. Therefore, we investigated the role of CRK-II serine 41 phosphorylation in the down-regulation of p120-catenin, cell motility and cell invasiveness in NSCLC cells. For this purpose, we expressed phosphomimetic and phosphodeficient CRK-II serine 41 mutants in NSCLC cells. NSCLC cells expressing phosphomimetic CRK-II seine 41 mutant showed lower p120-catenin level while CRK-II seine 41 phosphodeficient mutant expression resulted in higher p120-catenin. In addition, A549 cells expressing CRK-II serine 41 phosphomimetic mutant demonstrated more aggressive behavior in wound healing and invasion assays and, on the contrary, expression of phosphodeficient CRK-II serine 41 mutant in A549 cells resulted in reduced cell motility and invasiveness. We also provide evidence that PAK1 mediates CRK-II serine 41 phosphorylation. RNAi mediated silencing of PAK1 increased p120-catenin level in A549 and H157 cells. Furthermore, PAK1 silencing decreased cell motility and invasiveness in A549 cells. These effects were abrogated in A549 cells expressing phosphomimetic CRK-II serine 41. In summary, these data provide evidence for the role of PAK1 in the promotion of cell motility, cell invasiveness and the down regulation of p120-catenin through CRK serine 41 phosphorylation in NSCLC cells. Source