Basal-like phenotype is not associated with patient survival in estrogen-receptor-negative breast cancers

INTRODUCTION: Basal-phenotype or basal-like breast cancers are characterized by basal epithelium cytokeratin (CK5/14/17) expression, negative estrogen receptor (ER) status and distinct gene expression signature. We studied the clinical and biological features of the basal-phenotype tumors determined by immunohistochemistry (IHC) and cDNA microarrays especially within the ER-negative subgroup. METHODS: IHC was used to evaluate the CK5/14 status of 445 stage II breast cancers. The gene expression signature of the CK5/14 immunopositive tumors was investigated within a subset (100) of the breast tumors (including 50 ER-negative tumors) with a cDNA microarray. Survival for basal-phenotype tumors as determined by CK5/14 IHC and gene expression signature was assessed. RESULTS: From the 375 analyzable tumor specimens, 48 (13%) were immunohistochemically positive for CK5/14. We found adverse distant disease-free survival for the CK5/14-positive tumors during the first years (3 years hazard ratio (HR) 2.23, 95% confidence interval (CI) 1.17 to 4.24, p = 0.01; 5 years HR 1.80, 95% CI 1.02 to 3.15, p = 0.04) but the significance was lost at the end of the follow-up period (10 years HR 1.43, 95% CI 0.84 to 2.43, p = 0.19). Gene expression profiles of immunohistochemically determined CK5/14-positive tumors within the ER-negative tumor group implicated 1,713 differently expressed genes (p < 0.05). Hierarchical clustering analysis with the top 500 of these genes formed one basal-like and a non-basal-like cluster also within the ER-negative tumor entity. A highly concordant classification could be constructed with a published gene set (Sorlie's intrinsic gene set, concordance 90%). Both gene sets identified a basal-like cluster that included most of the CK5/14-positive tumors, but also immunohistochemically CK5/14-negative tumors. Within the ER-negative tumor entity there was no survival difference between the non-basal and basal-like tumors as identified by immunohistochemical or gene-expression-based classification. CONCLUSION: Basal cytokeratin-positive tumors have a biologically distinct gene expression signature from other ER-negative tumors. Even if basal cytokeratin expression predicts early relapse among non-selected tumors, the clinical outcome of basal tumors is similar to non-basal ER-negative tumors. Immunohistochemically basal cytokeratin-positive tumors almost always belong to the basal-like gene expression profile, but this cluster also includes few basal cytokeratin-negative tumors

Regulation of Signaling at Regions of Cell-Cell Contact by Endoplasmic Reticulum-Bound Protein-Tyrosine Phosphatase 1B

Protein-tyrosine phosphatase 1B (PTP1B) is a ubiquitously expressed PTP that is anchored to the endoplasmic reticulum (ER). PTP1B dephosphorylates activated receptor tyrosine kinases after endocytosis, as they transit past the ER. However, PTP1B also can access some plasma membrane (PM)-bound substrates at points of cell-cell contact. To explore how PTP1B interacts with such substrates, we utilized quantitative cellular imaging approaches and mathematical modeling of protein mobility. We find that the ER network comes in close proximity to the PM at apparently specialized regions of cell-cell contact, enabling PTP1B to engage substrate(s) at these sites. Studies using PTP1B mutants show that the ER anchor plays an important role in restricting its interactions with PM substrates mainly to regions of cell-cell contact. In addition, treatment with PTP1B inhibitor leads to increased tyrosine phosphorylation of EphA2, a PTP1B substrate, specifically at regions of cell-cell contact. Collectively, our results identify PM-proximal sub-regions of the ER as important sites of cellular signaling regulation by PTP1B

Evaluation of antimicrobial activities of some organic acids on bacteria

No Abstract. Discovery and Innovation Vol. 17(1&2) 2005: 22-2

Blood chemistry, haematological indices and nutrient digestibility of starter turkeys fed macaroni waste meal as a replacement for maize

A 56-days experiment was carried out to study the effect of replacing macaroni waste meal (MWM) with maize on nutrient digestibility and blood chemistry of indigenous turkey starter. Ninety-six indigenous turkey poults with an average weight of 52 g were randomly assigned to four dietary treatments containing macaroni waste meal at 0%, 15%, 30% and 45% level as replacement for maize. Each treatment consist of 24 turkey poults replicated thrice with 8 turkeys per replicate. A three day metabolic study trial was carried out for nutrient digestibility determination. Blood samples were also collected for serum and haematological indices. Data collected were subjected to one way analysis of variance. Result showed that MWM at 15% had the highest values for packed cell volume, red blood cell, white blood cell while values recorded for serum uric acid and creatinine were significantly lower (P&lt;0.05) for the turkeys. The nutrient digestibility coefficient such as crude protein digestibility, nitrogen retention were not affected significantly (P&gt;0.05). However, the packed cell volume, red blood cell count, albumin, hemoglobin, total serum protein and serum glucose. It can be concluded that MWM could be incorporated into the diet of indigenous turkey starter at 15% level without any deleterious effect on nutrient digestibility and blood chemistry.Keywords: Nutrient digestibility, Blood chemistr

The potential interruptive effect of tinnitus-related distress on attention

Abstract The mechanism through which tinnitus affects attention is unclear. This study examines whether distress mediates the relationship(s) between tinnitus and sustained, selective and executive attentions as well as response inhibition. Eighteen participants with tinnitus and fifteen controls completed the Counting Stroop, Vigilance and Stop Signal tasks. Tinnitus distress was assessed using the Tinnitus Questionnaire (TQ), severity of depressive mood states examined using the Beck Depression Inventory-II, and general distress assessed using the Hospital Anxiety and Depression Scale. Tinnitus participants had significantly slower reactions during the Vigilance task (F = 4.86, p = .035), and incongruent trials of the Cognitive Counting task (F = 3.45, p = .045) compared to controls. Tinnitus-related distress significantly mediated the effect of tinnitus in incongruent trials (TQ: Sobel test t = 1.73, p = .042) of the Cognitive Counting Task. Complaints of distress and concentration difficulties are common amongst tinnitus patients in clinical settings and these afflictions have been shown to negatively impact an individual’s quality of life. If confirmed in future studies, results suggest that distress may be an important factor in the causal mechanism between tinnitus and attention