BackgroundGene expression profiling of breast cancer has identified two biologically distinct estrogen receptor (ER)-positive subtypes of breast cancer: luminal A and luminal B. Luminal B tumors have higher proliferation and poorer prognosis than luminal A tumors. In this study, we developed a clinically practical immunohistochemistry assay to distinguish luminal B from luminal A tumors and investigated its ability to separate tumors according to breast cancer recurrence-free and disease-specific survival.MethodsTumors from a cohort of 357 patients with invasive breast carcinomas were subtyped by gene expression profile. Hormone receptor status, HER2 status, and the Ki67 index (percentage of Ki67-positive cancer nuclei) were determined immunohistochemically. Receiver operating characteristic curves were used to determine the Ki67 cut point to distinguish luminal B from luminal A tumors. The prognostic value of the immunohistochemical assignment for breast cancer recurrence-free and disease-specific survival was investigated with an independent tissue microarray series of 4046 breast cancers by use of Kaplan–Meier curves and multivariable Cox regression.ResultsGene expression profiling classified 101 (28%) of the 357 tumors as luminal A and 69 (19%) as luminal B. The best Ki67 index cut point to distinguish luminal B from luminal A tumors was 13.25%. In an independent cohort of 4046 patients with breast cancer, 2847 had hormone receptor–positive tumors. When HER2 immunohistochemistry and the Ki67 index were used to subtype these 2847 tumors, we classified 1530 (59%, 95% confidence interval [CI] = 57% to 61%) as luminal A, 846 (33%, 95% CI = 31% to 34%) as luminal B, and 222 (9%, 95% CI = 7% to 10%) as luminal–HER2 positive. Luminal B and luminal–HER2-positive breast cancers were statistically significantly associated with poor breast cancer recurrence-free and disease-specific survival in all adjuvant systemic treatment categories. Of particular relevance are women who received tamoxifen as their sole adjuvant systemic therapy, among whom the 10-year breast cancer–specific survival was 79% (95% CI = 76% to 83%) for luminal A, 64% (95% CI = 59% to 70%) for luminal B, and 57% (95% CI = 47% to 69%) for luminal–HER2 subtypes.ConclusionExpression of ER, progesterone receptor, and HER2 proteins and the Ki67 index appear to distinguish luminal A from luminal B breast cancer subtypes.

significant differences between axon-bearing and ax-presented (abstract 291.5) at the 29th Meeting of the 26. A. 8. Ali and A. M. Thomson,]. ~h~s i o l . (london) 507, on-lacking dendrites.Abscisic acid (ABA) stimulates stomatal closure and thus supports water conservation by plants during drought. Mass spectrometry-generated peptide sequence information was used t o clone a Vicia faba complementary DNA, AAPK, encoding a guard cell-specific ABA-activated serine-threonine protein kinase (AAPK). Expression in transformed guard cells of AAPK altered by one amino acid (lysine 43 t o alanine 43) renders stomata insensitive t o ABA-induced closure by eliminating ABA activation of plasma membrane anion channels. This information should allow cell-specific, targeted biotechnological manipulation of crop water status.

Context. Australia has a lamentable history of mammal extinctions. Until recently, the mammal fauna of northern Australia was presumed to have been spared such loss, and to be relatively intact and stable. However, several recent studies have suggested that this mammal fauna may be undergoing some decline, so a targeted monitoring program was established in northern Australia’s largest and best-resourced conservation reserve. Aims. The present study aims to detect change in the native small-mammal fauna of Kakadu National Park, in the monsoonal tropics of northern Australia, over the period of 1996–2009, through an extensive monitoring program, and to consider factors that may have contributed to any observed change. Methods. The small-mammal fauna was sampled in a consistent manner across a set of plots established to represent the environmental variation and fire regimes of Kakadu. Fifteen plots were sampled three times, 121 plots sampled twice and 39 plots once. Resampling was typically at 5-yearly intervals. Analysis used regression (of abundance against date), and Wilcoxon matched-pairs tests to assess change. For resampled plots, change in abundance of mammals was related to fire frequency in the between-sampling period. Key results. A total of 25 small mammal species was recorded. Plot-level species richness and total abundance decreased significantly, by 54% and 71%, respectively, over the course of the study. The abundance of 10 species declined significantly, whereas no species increased in abundance significantly. The number of ‘empty’ plots increased from 13% in 1996 to 55% in 2009. For 136 plots sampled in 2001–04 and again in 2007–09, species richness declined by 65% and the total number of individuals declined by 75%. Across plots, the extent of decline increased with increasing frequency of fire. The most marked declines were for northern quoll, Dasyurus hallucatus, fawn antechinus, Antechinus bellus, northern brown bandicoot, Isoodon macrourus, common brushtail possum, Trichosurus vulpecula, and pale field-rat, Rattus tunneyi. Conclusions. The native mammal fauna of Kakadu National Park is in rapid and severe decline. The cause(s) of this decline are not entirely clear, and may vary among species. The most plausible causes are too frequent fire, predation by feral cats and invasion by cane toads (affecting particularly one native mammal species). Implications. The present study has demonstrated a major decline in a key conservation reserve, suggesting that the mammal fauna of northern Australia may now be undergoing a decline comparable to the losses previously occurring elsewhere in Australia. These results suggest that there is a major and urgent conservation imperative to more precisely identify, and more effectively manage, the threats to this mammal fauna.

Doxorubicin is considered to be the most effective agent in the treatment of breast cancer patients. Unfortunately, resistance to this agent is common, representing a major obstacle to successful treatment. The identification of novel biomarkers that are able to predict treatment response may allow therapy to be tailored to individual patients. Antibody microarrays provide a powerful new technique, enabling the global comparative analysis of many proteins simultaneously. This technology may identify a panel of proteins to discriminate between drug-resistant and drug-sensitive samples. The Panorama Cell Signaling Antibody Microarray was exploited to analyze the MDA-MB-231 breast cancer cell line and a novel derivative, which displays significant resistance to doxorubicin at clinically relevant concentrations. The microarray comprised 224 antibodies selected from a variety of pathways, including apoptotic and cell signaling pathways. A standard z2.0-fold cutoff value was used to determine differentially expressed proteins. A decrease in the expression of mitogen-activated protein kinaseactivated monophosphotyrosine (phosphorylated extracellular signal-regulated kinase; 2.8-fold decrease), cyclin D2 (2.5-fold decrease), cytokeratin 18 (2.5-fold decrease), cyclin B1 (2.4-fold decrease), and heterogeneous nuclear ribonucleoprotein m3-m4 (2.0-fold decrease) was associated with doxorubicin resistance. Western blotting was exploited to confirm results from the antibody microarray experiment. These results suggest that antibody microarrays can be used to identify novel biomarkers and further validation may reveal mechanisms of chemotherapy resistance and identify potential therapeutic targets.