PIK3CA mutations in in situ and invasive breast carcinomas.

The PIK3 signaling pathway has been identified as one of the most important and most frequently mutated pathways in breast cancer. Somatic mutations in the catalytic subunit of PIK3CA have been found in a significant fraction of breast carcinomas, and it has been proposed that mutant PIK3CA plays a role in tumor initiation. However, the majority of primary human tumors analyzed for genetic alterations in PIK3CA have been invasive breast carcinomas and the frequency of PIK3CA mutations in preinvasive lesions has not been explored. To investigate this, we sequenced exons 9 and 20 of PIK3CA in pure ductal carcinoma in situ (DCIS), DCIS adjacent to invasive carcinoma, and invasive ductal breast carcinomas. In a subset of cases, both in situ and invasive areas were analyzed from the same tumor. We found that the frequency of PIK3CA mutations was essentially the same ( approximately 30%) in all three histologic groups. In some cases, in situ and invasive areas of the same tumor were discordant for PIK3CA status, and in two cases in which multiple invasive and adjacent in situ areas within the same tumor were analyzed independently, we detected intratumor heterogeneity for PIK3CA mutations. Our results suggest that mutation of PIK3CA is an early event in breast cancer that is more likely to play a role in breast tumor initiation than in invasive progression, although a potential role for exon 9 mutations in the progression of a subset of DCIS cases cannot be excluded.

Toxicity of carbon nanotubes to the activated sludge process.

The discharge of carbon nanotubes (CNTs) from industrial waste or disposal of such materials from commercial and/or domestic use will inevitably occur with increasing production and enter into wastewater treatment facilities with unknown consequences. Therefore, a better knowledge of the toxicity of CNTs to biological processes in wastewater treatment will be critical. This study examined the toxicity of multi-walled carbon nanotubes (MWCNTs) on the microbial communities in activated sludge. A comparative study using the activated sludge respiration inhibition test was performed on both unsheared mixed liquor and sheared mixed liquor to demonstrate the potential toxicity posed by MWCNTs and to illustrate the extent of extracellular polymeric substances (EPS) in protecting the microorganisms from the toxicity of CNTs. Respiration inhibition was observed for both unsheared and sheared mixed liquor when MWCNTs were present, however, greater respiration inhibition was observed for the sheared mixed liquor. The toxicity observed by the respiration inhibition test was determined to be dose-dependent; the highest concentration of MWCNTs exhibited the highest respiration inhibition. Scanning Electron Microscopy (SEM) images demonstrated direct physical contact between MWCNTs and activated sludge flocs.

Profiling critical cancer gene mutations in clinical tumor samples.

BACKGROUND: Detection of critical cancer gene mutations in clinical tumor specimens may predict patient outcomes and inform treatment options; however, high-throughput mutation profiling remains underdeveloped as a diagnostic approach. We report the implementation of a genotyping and validation algorithm that enables robust tumor mutation profiling in the clinical setting. METHODOLOGY: We developed and implemented an optimized mutation profiling platform ("OncoMap") to interrogate approximately 400 mutations in 33 known oncogenes and tumor suppressors, many of which are known to predict response or resistance to targeted therapies. The performance of OncoMap was analyzed using DNA derived from both frozen and FFPE clinical material in a diverse set of cancer types. A subsequent in-depth analysis was conducted on histologically and clinically annotated pediatric gliomas. The sensitivity and specificity of OncoMap were 93.8% and 100% in fresh frozen tissue; and 89.3% and 99.4% in FFPE-derived DNA. We detected known mutations at the expected frequencies in common cancers, as well as novel mutations in adult and pediatric cancers that are likely to predict heightened response or resistance to existing or developmental cancer therapies. OncoMap profiles also support a new molecular stratification of pediatric low-grade gliomas based on BRAF mutations that may have immediate clinical impact. CONCLUSIONS: Our results demonstrate the clinical feasibility of high-throughput mutation profiling to query a large panel of "actionable" cancer gene mutations. In the future, this type of approach may be incorporated into both cancer epidemiologic studies and clinical decision making to specify the use of many targeted anticancer agents.

Examination of purified single-walled carbon nanotubes on activated sludge process using batch reactors.

This paper evaluated the impact of over 90% purified single-walled carbon nanotubes (SWCNTs) on the activated sludge wastewater treatment process through a batch-scale study. We found that SWCNTs adsorbed 16.9% of the soluble COD (sCOD, soluble chemical oxygen demand) without activated sludge present. Statistical analysis of the experimental data demonstrated that only four experimental parameters, i.e., surface charge, sCOD, mixed liquor suspended solids, and sludge volume index were significantly impacted by the addition of SWCNTs; other parameters such as pH, dissolved oxygen, specific resistance to filtration, and relative hydrophobicity were not significantly impacted. Further examination of the four affected parameters illustrated that SWCNTs improved sludge settleability and made the surface of the activated sludge flocs less negatively charged. The addition of SWCNTs appeared to improve sCOD removal due mostly to absorption. This research also found that the impacts observed were from the SWCNTs, not the impurities within the SWCNTs tested.