Estimation of Measurement Uncertainty in Quantitation of Benzoylecgonine (BZE) and 11-nor-Δ9-THC-9-carboxylic acid (THCA).

Calculating measurement uncertainty is a helpful exercise for identifying components or steps in a forensic analytical procedure that contribute to measurement variance. In this study, we used a bottom up approach to identify components in our procedures that contribute to measurement variance in our Department of Defense (DoD) Drug Demand Reduction Program (DDRP) Gas Chromatography Mass Spectroscopy (GCMS) analytical procedures for benzoylecgonine (BZE) and the THC metabolite, 11-nor-Δ9-THC-9-carboxylic acid (THCA) at 125% the DDRP concentration threshold (cutoff). Each assay was run 10 times over 30 days, each assay containing five calibrators and five samples (125%).

Comparison of LC-MS-MS and GC-MS Analysis of Benzodiazepine Compounds Included in the Drug Demand Reduction Urinalysis Program.

Liquid chromatography-tandem mass spectrometry (LC-MS-MS) offers specific advantages over gas chromatography-mass spectrometry (GC-MS) such as the ability to identify and measure a broader range of compounds with minimal sample preparation. Comparative analysis of LC-MS-MS versus GC-MS was performed for urinalysis detection of five benzodiazepine compounds currently part of the Department of Defense (DoD) Drug Demand Reduction Program (DDRP) testing panel; alpha-hydroxyalprazolam, oxazepam, lorazepam, nordiazepam and temazepam. In the analyses of internally prepared control urine samples at concentrations around the DDRP administrative decision point for benzodiazepines (100 ng/mL), both technologies produced comparable results with average accuracies between 99.

Tumor intrinsic subtype is reflected in cancer-adjacent tissue.

Introduction: Overall survival of early-stage breast cancer patients is similar for those who undergo breast-conserving therapy (BCT) and mastectomy; however, 10% to 15% of women undergoing BCT suffer ipsilateral breast tumor recurrence. The risk of recurrence may vary with breast cancer subtype. Understanding the gene expression of the cancer-adjacent tissue and the stromal response to specific tumor subtypes is important for developing clinical strategies to reduce recurrence risk.

Role of HGF in epithelial-stromal cell interactions during progression from benign breast disease to ductal carcinoma in situ.

Introduction: Basal-like and luminal breast cancers have distinct stromal-epithelial interactions, which play a role in progression to invasive cancer. However, little is known about how stromal-epithelial interactions evolve in benign and pre-invasive lesions.

Methods: To study epithelial-stromal interactions in basal-like breast cancer progression, we cocultured reduction mammoplasty fibroblasts with the isogenic MCF10 series of cell lines (representing benign/normal, atypical hyperplasia, and ductal carcinoma in situ).

Impact of tumor microenvironment and epithelial phenotypes on metabolism in breast cancer.

Purpose: Cancer cells have altered metabolism, with increased glucose uptake, glycolysis, and biomass production. This study conducted genomic and metabolomic analyses to elucidate how tumor and stromal genomic characteristics influence tumor metabolism.

Experimental Design: Thirty-three breast tumors and six normal breast tissues were analyzed by gene expression microarray and by mass spectrometry for metabolites.

Gene expression in extratumoral microenvironment predicts clinical outcome in breast cancer patients.

Introduction: A gene expression signature indicative of activated wound responses is common to more than 90% of non-neoplastic tissues adjacent to breast cancer, but these tissues also exhibit substantial heterogeneity. We hypothesized that gene expression subtypes of breast cancer microenvironment can be defined and that these microenvironment subtypes have clinical relevance.

Methods: Gene expression was evaluated in 72 patient-derived breast tissue samples adjacent to invasive breast cancer or ductal carcinoma in situ.

Interactions with fibroblasts are distinct in Basal-like and luminal breast cancers.

Basal-like breast cancers have several well-characterized distinguishing molecular features, but most of these are features of the cancer cells themselves. The unique stromal-epithelial interactions, and more generally, microenvironmental features of basal-like breast cancers have not been well characterized. To identify characteristic microenvironment features of basal-like breast cancer, we performed cocultures of several basal-like breast cancer cell lines with fibroblasts and compared these with cocultures of luminal breast cancer cell lines with fibroblasts.

Activation of host wound responses in breast cancer microenvironment.

Purpose: Cancer progression is mediated by processes that are also important in wound repair. As a result, cancers have been conceptualized as overhealing wounds or "wounds that do not heal," and gene expression signatures reflective of wound repair have shown value as predictors of breast cancer survival. Despite the widespread acknowledgment of commonalities between host responses to wounds and host responses to cancer, the gene expression responses of normal tissue adjacent to cancers have not been well characterized.