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A study was conducted to evaluate the association between mutations and the result of erlotinib treatment and the feasibility of mass screening for the presence of epidermal growth factor receptor gene (EGFR). Results revealed that mass screening of patients with lung cancer with EGFR gene mutations is possible and could have an impact in decisions relevant to treatment.

Abstract Background Metastatic non-small-cell lung cancer (NSCLC) has a dismal prognosis. EGFR is overexpressed or mutated in a large proportion of cases. Downstream components of the EGFR pathway and crosstalk with the NF-κB pathway have not been examined at the clinical level. We explored the prognostic significance of the mRNA expression of nine genes in the EGFR and NF-κB pathways and of BRCA1 and RAP80 in patients in whom EGFR and K-ras gene status had previously been determined. In addition, NFKBIA and DUSP22 gene status was also determined. Methods mRNA expression of the eleven genes was determined by QPCR in 60 metastatic NSCLC patients and in nine lung cancer cell lines. Exon 3 of NFKBIA and exon 6 of DUSP22 were analyzed by direct sequencing. Results were correlated with outcome to platinum-based chemotherapy in patients with wild-type EGFR and to erlotinib in those with EGFR mutations. Results BRCA1 mRNA expression was correlated with EZH2, AEG-1, Musashi-2, CYLD and TRAF6 expression. In patients with low levels of both BRCA1 and AEG-1, PFS was 13.02 months, compared to 5.4 months in those with high levels of both genes and 7.7 months for those with other combinations (P = 0.025). The multivariate analysis for PFS confirmed the prognostic role of high BRCA1/AEG-1 expression (HR, 3.1; P = 0.01). Neither NFKBIA nor DUSP22 mutations were found in any of the tumour samples or cell lines. Conclusions The present study provides a better understanding of the behaviour of metastatic NSCLC and identifies the combination of BRCA1 and AEG-1 expression as a potential prognostic model.

Abstract Background Immunohistochemistry (IHC) with mutation-specific antibodies may be an ancillary method of detecting EGFR mutations in lung cancer patients. Methods EGFR mutation status was analyzed by DNA assays, and compared with IHC results in five non-small-cell lung cancer (NSCLC) cell lines and tumor samples from 78 stage IV NSCLC patients. Results IHC correctly identified del 19 in the H1650 and PC9 cell lines, L858R in H1975, and wild-type EGFR in H460 and A549, as well as wild-type EGFR in tumor samples from 22 patients. IHC with the mAb against EGFR with del 19 was highly positive for the protein in all 17 patients with a 15-bp (ELREA) deletion in exon 19, whereas in patients with other deletions, IHC was weakly positive in 3 cases and negative in 9 cases. IHC with the mAb against the L858R mutation showed high positivity for the protein in 25/27 (93%) patients with exon 21 EGFR mutations (all with L858R) but did not identify the L861Q mutation in the remaining two patients. Conclusions IHC with mutation-specific mAbs against EGFR is a promising method for detecting EGFR mutations in NSCLC patients. However these mAbs should be validated with additional studies to clarify their possible role in routine clinical practice for screening EGFR mutations in NSCLC patients.

Review of literature on gender-linked aspects of nonverbal behavior reveals that the differences in nonverbal behavior are in line with societal expectations calling for women to be reactive and for men to be proactive. Communication between the sexes is discussed in terms of smiling, personal space, touch, and talk. (JMF)

The EURTAC trial demonstrated that the tyrosine kinase inhibitor (TKI) erlotinib was superior to chemotherapy as first-line therapy for advanced non-small cell lung cancers (NSCLC) that harbor EGFR activating mutations in a predominantly Caucasian population. Based on EURTAC and several Asian trials, anti-EGFR TKIs are standard of care for EGFR mutation-positive NSCLC. We sought to validate a rapid multiplex EGFR mutation assay as a companion diagnostic assay to select patients for this therapy. Samples from the EURTAC trial were prospectively screened for EGFR mutations using a combination of laboratory-developed tests (LDTs), and tested retrospectively with the cobas EGFR mutation test (EGFR PCR test). The EGFR PCR test results were compared to the original LDT results and to Sanger sequencing, using a subset of specimens from patients screened for the trial. Residual tissue was available from 487 (47%) of the 1044 patients screened for the trial. The EGFR PCR test showed high concordance with LDT results with a 96.3% overall agreement. The clinical outcome of patients who were EGFR-mutation detected by the EGFR PCR test was very similar to the entire EURTAC cohort. The concordance between the EGFR PCR test and Sanger sequencing was 90.6%. In 78.9% of the discordant samples, the EGFR PCR test result was confirmed by a sensitive deep sequencing assay. This retrospective study demonstrates the clinical utility of the EGFR PCR test in the accurate selection of patients for anti-EGFR TKI therapy. The EGFR PCR test demonstrated improved performance relative to Sanger sequencing. [ABSTRACT FROM AUTHOR]

Tumor cell dedifferentiation—such as the loss of cell-to-cell adhesion in epithelial tumors—is associated with tumor progression. To better understand the mechanisms that maintain carcinoma cells in a differentiated state, we have dissected in vitro differentiation pathways in the mucus-secretor HT-29 M6 colon cancer cell line, which spontaneously differentiates in postconfluent cultures. By lowering the extracellular calcium concentration to levels that prevent intercellular adhesion and epithelial polarization, our results reveal that differentiation is calcium-dependent and involves: (i) a process of cell cycle exit to G0 and (ii) the induction of a transcriptional program of differentiation gene expression (i.e., mucins MUC1 and MUC5AC, and the apical membrane peptidase DPPIV). In calcium-deprived, non-differentiated postconfluent cultures, differentiation gene promoters are repressed by a trichostatin A (TSA)-sensitive mechanism, indicating that loss of gene expression by dedifferentiation is driven by histone deacetylases (HDAC). Since TSA treatment or extracellular calcium restoration allow gene promoter activation to similar levels, we suggest that induction of differentiation is one mechanism of HDAC inhibitor antitumor action. Moreover, transcriptional de-repression can also be induced in non-differentiating culture conditions by overexpressing the cyclin-dependent kinase inhibitor p27KIP1, which is normally induced during spontaneous differentiation. Since p27KIP1 downregulation in colon cancer is associated with poor prognosis independently of tumor cell division rates, we propose that p27 KIP1 may prevent tumor progression by, at least in part, enhancing the expression of some differentiation genes. Therefore, the HT-29 M6 model allows the identification of some basic mechanisms of cancer cell differentiation control, so far revealing HDAC and p27KIP1 as key regulatory factors of differentiation gene expression. J. Cell. Physiol. 212: 42–50, 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

This article permits the observation of informal, social interaction processes that operate in communication. In this experiment the effects of social interaction and sex differences call for reexamination and extension of the concepts of independence and saturation of communication networks. Independence and saturation appear to be interdependent rather than separate processes; their mutual dependence is revealed when social interaction variables are allowed to operate. The interaction between sex and experimental condition found in the study suggests the importance of congruence between preferred modes of interacting and the structural requirements of the communication situation. In the interaction of sex and condition, the differential responses made by males and females to the requirements of problem solving in a social a social milieu are revealed. The face-to-face condition enhanced the efficiency and satisfaction of males and impede the efficiency and satisfaction of females. If the female Ss were attending more to social interaction than to the task, the competing cues would result in less efficient performance. Alternately, sex role conflict might inhere in public achievement in a competitive situation and lead to poorer performance.

This article presents information on school racial integration. There have been a variety of recent controversies, both over the issue of bussing school children to obtain quality education for Black children in integrated schools and over the results of attempts to evaluate the effects of bussing as a means to school integration and quality education. Often the two issues are not unrelated. Moreover, the motivations of the politicians, educators, social scientists, school board members and others with vested interests who are engaged in these controversies, while often quite clear, are at other times concealed behind a jungle of rationalizations. Modern day supporters and opponents of school integration point to the Supreme Court Decision of 1954 as the crucial historic and triggering event in developments leading to the present controversy over the rightness or wrongness of integration. Both sides do the Supreme Court a disservice. It makes far more sense to consider--as far as the United States is concerned--the full history of racism in the country as the background of the present controversy.