A Critical Analysis of Rural Teachers\u27 Usage of Online Communities

The purpose of this study was to analyze data related to rural teachers\u27 use of online communities. Rural teachers are often isolated in their practice and sometimes have difficulty connecting with other teachers with their same assignments or needs due to their professional setting. As Internet availability increases and online communities proliferate, teachers have more opportunity than ever to seek personal and professional support in virtual relationships when face-to-face ones are not easily available. In small schools such as the ones included in this study, teachers can become burned out as they perform the difficult task of teaching with few colleagues in their department or grade level to turn to for support. One interview subject said that she and the only other person with the same teaching assignment don\u27t always have time to communicate and often have to use their lunch period to do so. Another said that she feels very isolated because there are only three of them with the same grade level assignment. The most telling comment came from one high school teacher, I am the foreign language department. In spite of these expressed feelings of isolation, this study\u27s results do not support widespread use of online communities by these particular rural teachers to help fill their personal and professional needs. The only online communication technology widely used was email. At a minimum, every subject in this study had access to a high-speed Internet connection, functional technology, administrative support, and training. With this type of support already in place, further study is needed to discover what would increase awareness and use of online communities by this group of teachers. Additionally, similar studies in different rural school settings might show different results. Comparisons of study findings between rural schools in different geographic locations would be revealing. Such comparative studies could help inform administrators and online community developers who wish to better meet the needs of rural teachers

Aromatase inhibition remodels the clonal architecture of estrogen-receptor-positive breast cancers

Resistance to oestrogen-deprivation therapy is common in oestrogen-receptor-positive (ER+) breast cancer. To better understand the contributions of tumour heterogeneity and evolution to resistance, here we perform comprehensive genomic characterization of 22 primary tumours sampled before and after 4 months of neoadjuvant aromatase inhibitor (NAI) treatment. Comparing whole-genome sequencing of tumour/normal pairs from the two time points, with coincident tumour RNA sequencing, reveals widespread spatial and temporal heterogeneity, with marked remodelling of the clonal landscape in response to NAI. Two cases have genomic evidence of two independent tumours, most obviously an ER− ‘collision tumour', which was only detected after NAI treatment of baseline ER+ disease. Many mutations are newly detected or enriched post treatment, including two ligand-binding domain mutations in ESR1. The observed clonal complexity of the ER+ breast cancer genome suggests that precision medicine approaches based on genomic analysis of a single specimen are likely insufficient to capture all clinically significant information

PIK3CA and PIK3CB Inhibition Produce Synthetic Lethality when Combined with Estrogen Deprivation in Estrogen Receptor-Positive Breast Cancer

Several phosphoinositide-3-kinase (PI3K) catalytic subunit inhibitors are currently in clinical trial. We therefore sought to examine relationships between pharmacological inhibition and somatic mutations in PI3K catalytic subunits in ER+ breast cancer, where these mutations are particularly common. RNA interference (RNAi) was used to determine the effect of selective inhibition of PI3K catalytic subunits, p110α and p110β, in ER+ breast cancer cells harboring either mutation (PIK3CA) or gene amplification (PIK3CB). p110α RNAi inhibited growth and promoted apoptosis in all tested ER+ breast cancer cells under estrogen deprived-conditions, whereas p110β RNAi only affected cells harboring PIK3CB amplification. Moreover, dual p110α/p110β inhibition potentiated these effects. In addition, treatment with the clinical grade PI3K catalytic subunit inhibitor BEZ235 also promoted apoptosis in ER+ breast cancer cells. Importantly, estradiol suppressed apoptosis induced by both gene knockdowns and by BEZ235 treatment. Our results suggest that PI3K inhibitors should target both p110α and p110β catalytic subunits, whether wild-type or mutant, and be combined with endocrine therapy for maximal efficacy when treating ER+ breast cancer

Genome remodelling in a basal-like breast cancer metastasis and xenograft

Massively parallel DNA sequencing technologies provide an unprecedented ability to screen entire genomes for genetic changes associated with tumour progression. Here we describe the genomic analyses of four DNA samples from an African-American patient with basal-like breast cancer: peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The metastasis contained two de novo mutations and a large deletion not present in the primary tumour, and was significantly enriched for 20 shared mutations. The xenograft retained all primary tumour mutations and displayed a mutation enrichment pattern that resembled the metastasis. Two overlapping large deletions, encompassing CTNNA1, were present in all three tumour samples. The differential mutation frequencies and structural variation patterns in metastasis and xenograft compared with the primary tumour indicate that secondary tumours may arise from a minority of cells within the primary tumour