A reason why the ERBB2 gene is amplified and not mutated in breast cancer

Alterations of receptor-type tyrosine kinases (RTK) are frequent in human cancers. They can result from translocation, mutation or amplification. The ERBB2 RTK is encoded by a gene that is amplified in about 20% breast cancers. The question is: why is this RTK specifically subjected to this type of alteration? We propose that ERBB2 gene amplification is used to overcome repression of its expression by sequence-specific transcription factors

Exercise Training for autoimmune myasthenia gravis: A review of safety and effectiveness based on existing literature

No abstract is required for a review article as per instruction

The RD Parent Empowerment Program Creates Measurable Change in the Behaviors of Low-Income Families and Children: An Intervention Description and Evaluation

Dietary and physical activity habits are developed early in life and are influenced by family environments. We describe and evaluate an intervention for low-income families to encourage healthy habits. The RD Parent Empowerment Program (http://www.eatright.org/programs/kidseatright/activities/content.aspx?id=6442477891) consists of four workshops centered on the 8 Habits of Healthy Children and Families (Academy of Nutrition and Dietetics Foundation). Registered dietitian nutritionists conduct the workshops in school and community settings using a structured leader guide and tailor the communication and interactive activities to the audience. Participants are parents of young children. Our goals were to use a phenomenologic approach to elicit participant feedback, determine whether participants in the RD Parent Empowerment Program made healthier choices for their families after attending the workshops, and identify which elements of the program participants believed contributed most to its success. The evaluation design used a pragmatic, mixed-methods approach utilizing postintervention focus groups and pre–post-intervention scores on the Family Nutrition and Physical Activity (FNPA) survey. All workshop attendees aged 18 years or older were eligible to participate in the evaluation. One hundred twenty-three parents participated in the intervention across seven sites. Focus group results were analyzed using thematic analysis methods to match themes to the main intervention goals. t-Tests were used to compare pre-and post-intervention FNPA scores and demographic characteristics pooled across sites. FNPA scores significantly improved from pre- to postintervention by a mean of 4.3 FNPA points (6.5%; P\u3c0.01). Focus group participants reported behavior changes as a result of the program and identified the site leaders as integral to the program’s success, triangulating the results. The RD Parent Empowerment Program generates meaningful self-reported behavior change in parents. The long-term sustainability of the changes must be investigated

The RD Parent Empowerment Program Creates Measurable Change in the Behaviors of Low-Income Families and Children: An Intervention Description and Evaluation

Dietary and physical activity habits are developed early in life and are influenced by family environments. We describe and evaluate an intervention for low-income families to encourage healthy habits. The RD Parent Empowerment Program (http://www.eatright.org/programs/kidseatright/activities/content.aspx?id=6442477891) consists of four workshops centered on the 8 Habits of Healthy Children and Families (Academy of Nutrition and Dietetics Foundation). Registered dietitian nutritionists conduct the workshops in school and community settings using a structured leader guide and tailor the communication and interactive activities to the audience. Participants are parents of young children. Our goals were to use a phenomenologic approach to elicit participant feedback, determine whether participants in the RD Parent Empowerment Program made healthier choices for their families after attending the workshops, and identify which elements of the program participants believed contributed most to its success. The evaluation design used a pragmatic, mixed-methods approach utilizing postintervention focus groups and pre–post-intervention scores on the Family Nutrition and Physical Activity (FNPA) survey. All workshop attendees aged 18 years or older were eligible to participate in the evaluation. One hundred twenty-three parents participated in the intervention across seven sites. Focus group results were analyzed using thematic analysis methods to match themes to the main intervention goals. t-Tests were used to compare pre- and postintervention FNPA scores and demographic characteristics pooled across sites. FNPA scores significantly improved from pre- to postintervention by a mean of 4.3 FNPA points (6.5%; P\u3c0.01). Focus group participants reported behavior changes as a result of the program and identified the site leaders as integral to the program’s success, triangulating the results. The RD Parent Empowerment Program generates meaningful self-reported behavior change in parents. The long-term sustainability of the changes must be investigated

Down-Regulation of ECRG4, a Candidate Tumor Suppressor Gene, in Human Breast Cancer

INTRODUCTION: ECRG4/C2ORF40 is a potential tumor suppressor gene (TSG) recently identified in esophageal carcinoma. Its expression, gene copy number and prognostic value have never been explored in breast cancer. METHODS: Using DNA microarray and array-based comparative genomic hybridization (aCGH), we examined ECRG4 mRNA expression and copy number alterations in 353 invasive breast cancer samples and normal breast (NB) samples. A meta-analysis was done on a large public retrospective gene expression dataset (n = 1,387) in search of correlations between ECRG4 expression and histo-clinical features including survival. RESULTS: ECRG4 was underexpressed in 94.3% of cancers when compared to NB. aCGH data revealed ECRG4 loss in 18% of tumors, suggesting that DNA loss is not the main mechanism of underexpression. Meta-analysis showed that ECRG4 expression was significantly higher in tumors displaying earlier stage, smaller size, negative axillary lymph node status, lower grade, and normal-like subtype. Higher expression was also associated with disease-free survival (DFS; HR = 0.84 [0.76-0.92], p = 0.0002) and overall survival (OS; HR = 0.72 [0.63-0.83], p = 5.0E-06). In multivariate analysis including the other histo-clinical prognostic features, ECRG4 expression remained the only prognostic factor for DFS and OS. CONCLUSIONS: Our data suggest that ECRG4 is a candidate TSG in breast cancer, the expression of which may help improve the prognostication. If functional analyses confirm this TSG role, restoring ECRG4 expression in the tumor may represent a promising therapeutic approach

Interaction with the Phosphotyrosine Binding Domain/Phosphotyrosine Interacting Domain of SHC Is Required for the Transforming Activity of the FLT4/VEGFR3 Receptor Tyrosine Kinase

The FLT4 gene encodes two isoforms of a tyrosine kinase receptor, which belongs to the family of receptors for vascular endothelial growth factor. As the result of an alternative processing of primary mRNA transcripts, the long isoform differs from the short isoform by an additional stretch of 65 amino acid residues located at the C terminus and containing three tyrosine residues, Tyr1333, Tyr1337, and Tyr1363. Only the long isoform is endowed with a transforming capacity in fibroblasts. We show that this activity is related to the capacity of the tyrosine 1337-containing sequence to interact with the phosphotyrosine binding domain of the SHC protein. This demonstrates that a functional property of this newly described domain includes relay of mitogenic signals. In addition, it shows that the same receptor can mediate different functions through the optional binding of the phosphotyrosine binding domain and that the alternative use of this domain is sufficient to direct the signal toward different pathways

School functioning and violent behavior among young adolescents: a contextual analysis

This paper examines associations between overall school functioning and the frequency of violent behaviors among young adolescents (ages 10–14). The sample included 16 middle schools participating in an unrelated intervention study (on nutrition) in Minneapolis, Minnesota. A School Functioning Index developed to characterize schools’ overall stability, performance, and demographics was constructed using data from public archives and school administrator surveys. Data on violent behaviors and other variables were collected in student surveys in fall 1998 and spring 1999. We used multilevel modeling to assess the effect of school functioning on violent behavior after adjusting for known individual-level covariates of violent behaviors. We found an interaction between school functioning (group-level variable) and expectations for future education (individual-level variable). Among students who reported expectations of completing a college degree (71% of the sample), positive school functioning was negatively associated with violent behaviors. Among students that reported expectations of completing less than a college degree, no association was found between school functioning and violent behaviors. These results support earlier work suggesting that objectively measured school characteristics are associated with students’ violent behaviors even after accounting for individual-level factors and also identify a subgroup of students for whom school detachment may be an issue

FGFR1 and WT1 are markers of human prostate cancer progression

BACKGROUND: Androgen-independent prostate adenocarcinomas are responsible for about 6% of overall cancer deaths in men. METHODS: We used DNA microarrays to identify genes related to the transition between androgen-dependent and androgen-independent stages in the LuCaP 23.1 xenograft model of prostate adenocarcinoma. The expression of the proteins encoded by these genes was then assessed by immunohistochemistry on tissue microarrays (TMA) including human prostate carcinoma samples issued from 85 patients who had undergone radical prostatectomy. RESULTS: FGFR1, TACC1 and WT1 gene expression levels were associated with the androgen-independent stage in xenografts and human prostate carcinoma samples. MART1 protein expression was correlated with pT2 tumor stages. CONCLUSION: Our results suggest that each of these four genes may play a role, or at least reflect a stage of prostate carcinoma growth/development/progression