Association between Obesity, Race or Ethnicity, and Luminal Subtypes of Breast Cancer.

Luminal breast cancers are the most common genomic subtype of breast cancers where Luminal A cancers have a better prognosis than Luminal B. Exposure to sex steroids and inflammatory status due to obesity are key contributors of Luminal tumor development. In this study, 1928 patients with Luminal A breast cancer and 1610 patients with Luminal B breast cancer were compared based on body mass index (BMI), age, race, menopausal status, and expressed receptors (i.e., estrogen (ER), progesterone (PR), and human epidermal growth factor receptor 2 (HER2)). Patients with Luminal B tumors had a significantly higher mean BMI (Δ = 0.69 kgm−2 [0.17, 1.21], p = 0.010) versus Luminal A. Interestingly, the risks of Luminal B tumors were higher among Black/African American patients versus White and Hispanic patients (p < 0.001 and p = 0.001, respectively). When controlled for each other, Black/African American race (p < 0.001) and increased BMI (p = 0.008) were associated with increased risks of Luminal B carcinoma, while postmenopausal status was associated with a decreased risk (p = 0.028). Increased BMI partially mediated the strong association between Black/African American race and the risk of Luminal B carcinoma. Thus, Black/African American race along with obesity seem to be associated with an increased risk of more aggressive Luminal B breast carcinomas.

An evaluation of veterinary allergen extract content and resultant canine intradermal threshold concentrations.

BACKGROUND: Limited information is available for dogs on threshold concentrations (TCs), and the protein composition of common allergenic extracts produced by different manufacturers. HYPOTHESIS/OBJECTIVES: To characterize the protein heterogeneity of tree, grass, weed and mite allergens from different lots of allergenic extracts, and to determine intradermal TCs for healthy dogs using extracts from two manufacturers. ANIMALS: Twenty five privately owned, clinically healthy dogs and ten purpose-bred beagle dogs. METHODS AND MATERIALS: Protein concentration and heterogeneity of 11 allergens from two manufacturers were evaluated using a Bradford-style assay and SDS-PAGE. Intradermal testing was performed with 11 allergens from each company at four dilutions. Immediate reactions were subjectively scored (0 to 4+), and objectively measured (mm) and their percentage concordance evaluated. Model-based TCs were determined by fitting positive reactions (≥2+) at 15 min to generalized estimating equations. RESULTS: Allergen extract protein quantity and composition varied within and between manufacturers despite sharing the same PNU/mL values. Model-based TCs of one weed, five trees, two grasses and a house dust mite were determined for extracts from Manufacturer 1 (M1), and for extracts of three weeds, three trees and two grasses from Manufacturer 2 (M2). Receiver operating characteristic curve analyses determined a percentage concordance of the objective and subjective measurements of 77.3% for M1 and 75% for M2 allergens. CONCLUSIONS AND CLINICAL IMPORTANCE: Veterinary allergen extracts labelled as the same species and PNU/mL are not standardized; they show heterogeneity in composition and potency within and between manufacturers. Variability in extract content may require adjustment of intradermal testing concentrations.

Stat3 Signaling Promotes Survival And Maintenance Of Medullary Thymic Epithelial Cells.

Medullary thymic epithelial cells (mTECs) are essential for establishing central tolerance by expressing a diverse array of self-peptides that delete autoreactive thymocytes and/or divert thymocytes into the regulatory T cell lineage. Activation of the NFκB signaling pathway in mTEC precursors is indispensable for mTEC maturation and proliferation resulting in proper medullary region formation. Here we show that the Stat3-mediated signaling pathway also plays a key role in mTEC development and homeostasis. Expression of a constitutively active Stat3 transgene targeted to the mTEC compartment increases mTEC cellularity and bypasses the requirement for signals from positively selected thymocytes to drive medullary region formation. Conversely, conditional deletion of Stat3 disrupts medullary region architecture and reduces the number of mTECs. Stat3 signaling does not affect mTEC proliferation, but rather promotes survival of immature MHCIIloCD80lo mTEC precursors. In contrast to striking alterations in the mTEC compartment, neither enforced expression nor deletion of Stat3 affects cTEC cellularity or organization. These results demonstrate that in addition to the NFkB pathway, Stat3-mediated signals play an essential role in regulating mTEC cellularity and medullary region homeostasis.