Prognostic utility of the breast cancer index and comparison to Adjuvant! Online in a clinical case series of early breast cancer.

Introduction: Breast Cancer Index (BCI) combines two independent biomarkers, HOXB13:IL17BR (H:I) and the 5-gene molecular grade index (MGI), that assess estrogen-mediated signalling and tumor grade, respectively. BCI stratifies early-stage estrogen-receptor positive (ER+), lymph-node negative (LN-) breast cancer patients into three risk groups and provides a continuous assessment of individual risk of distant recurrence. Objectives of the current study were to validate BCI in a clinical case series and to compare the prognostic utility of BCI and Adjuvant!Online (AO).

Performance and clinical evaluation of the 92-gene real-time PCR assay for tumor classification.

Accurate determination of cancer origin is necessary to guide optimal treatment but remains a diagnostic challenge. Gene expression profiling technologies have aided the classification of tumors and, therefore, could be applied in conjunction with clinicopathologic correlates to improve accuracy. We report an expanded version of the previously described 92-gene assay to classify 30 main tumor types and 54 histological subtypes, with coverage of ≥95% of all solid tumors based on incidence.

Hormone-based therapies in the regulation of fuel metabolism and body weight.

Background: The integrated central actions of hormones secreted from pancreatic islets, the gut and adipocytes regulate both energy homeostasis and body weight. Dysregulation in these neurohormonal pathways probably contributes to pathogenesis of obesity and type 2 diabetes.

Objective: To examine hormone-based therapies targeting these interrelated pathways as potential treatments for obesity and diabetes.

Sustained weight loss following 12-month pramlintide treatment as an adjunct to lifestyle intervention in obesity.

Objective: To assess long-term weight loss efficacy and safety of pramlintide used at different dosing regimens and in conjunction with lifestyle intervention (LSI).

Research Design And Methods: In a 4-month, double-blind, placebo-controlled, dose-ranging study, 411 obese subjects were randomized to receive pramlintide (six arms: 120, 240, and 360 microg b.i.

Pramlintide treatment reduces 24-h caloric intake and meal sizes and improves control of eating in obese subjects: a 6-wk translational research study.

Evidence from rodent studies indicates that the beta-cell-derived neurohormone amylin exerts multiple effects on eating behavior, including reductions in meal size, intake of highly palatable foods, and stress-induced sucrose consumption. To assess the effect of amylin agonism on human eating behavior we conducted a randomized, blinded, placebo-controlled, multicenter study investigating the effects of the amylin analog pramlintide on body weight, 24-h caloric intake, portion sizes, "fast food" intake, and perceived control of eating in 88 obese subjects. After a 2-day placebo lead-in, subjects self-administered pramlintide (180 microg) or placebo by subcutaneous injection 15 min before meals for 6 wk without concomitant lifestyle modifications.

Progressive reduction in body weight after treatment with the amylin analog pramlintide in obese subjects: a phase 2, randomized, placebo-controlled, dose-escalation study.

Context: In previous 1-yr trials, treatment with pramlintide (120 microg), an analog of the beta-cell hormone amylin, induced sustained reductions in A1C and body weight in insulin-using subjects with type 2 diabetes.

Objective: To assess the potential of pramlintide as an antiobesity agent, we assessed the weight effect, safety, and tolerability of pramlintide in non-insulin-treated obese subjects with and without type 2 diabetes at doses greater than previously studied.

Design/setting: We performed a randomized, double-blind, placebo-controlled, multicenter study.

Pharmacokinetics of an oral drug (acetaminophen) administered at various times relative to subcutaneous injection of pramlintide in subjects with type 2 diabetes.

Pramlintide, an adjunct treatment to mealtime insulin for patients with type 2 and type 1 diabetes, aids glycemic control by suppressing postprandial glucagon secretion, slowing gastric emptying, and enhancing satiety. Because gastric emptying affects oral medication absorption, this placebo-controlled, single-blind, crossover study examined the absorption of 1000 mg of acetaminophen elixir administered -2, -1, 0, +1, and +2 hours relative to pramlintide (120 microg) or 0 hours relative to placebo in 24 patients with type 2 diabetes. When acetaminophen administration occurred 0, +1, or +2 hours relative to pramlintide, the maximum observed plasma concentration of acetaminophen decreased 14% to 29%, and time to maximum observed plasma concentration increased by 0.

Bacterial outer membrane vesicles and the host-pathogen interaction.

Extracellular secretion of products is the major mechanism by which Gram-negative pathogens communicate with and intoxicate host cells. Vesicles released from the envelope of growing bacteria serve as secretory vehicles for proteins and lipids of Gram-negative bacteria. Vesicle production occurs in infected tissues and is influenced by environmental factors.

Enterotoxigenic Escherichia coli vesicles target toxin delivery into mammalian cells.

Enterotoxigenic Escherichia coli (ETEC) is a prevalent cause of traveler's diarrhea and infant mortality in third-world countries. Heat-labile enterotoxin (LT) is secreted from ETEC via vesicles composed of outer membrane and periplasm. We investigated the role of ETEC vesicles in pathogenesis by analyzing vesicle association and entry into eukaryotic cells.

Incorporation of heterologous outer membrane and periplasmic proteins into Escherichia coli outer membrane vesicles.

Gram-negative bacteria shed outer membrane vesicles composed of outer membrane and periplasmic components. Since vesicles from pathogenic bacteria contain virulence factors and have been shown to interact with eukaryotic cells, it has been proposed that vesicles behave as delivery vehicles. We wanted to determine whether heterologously expressed proteins would be incorporated into the membrane and lumen of vesicles and whether these altered vesicles would associate with host cells.