11 research outputs found
Multigene assays and molecular markers in breast cancer: systematic review of health economic analyses
Visualization of Gli Activity in Craniofacial Tissues of Hedgehog-Pathway Reporter Transgenic Zebrafish
The Hedgehog (Hh)-signaling pathway plays a crucial role in the development and maintenance of multiple vertebrate and invertebrate organ systems. Gli transcription factors are regulated by Hh-signaling and act as downstream effectors of the pathway to activate Hh-target genes. Understanding the requirements for Hh-signaling in organisms can be gained by assessing Gli activity in a spatial and temporal fashion.We have generated a Gli-dependent (Gli-d) transgenic line, Tg(Gli-d:mCherry), that allows for rapid and simple detection of Hh-responding cell populations in both live and fixed zebrafish. This transgenic line expresses a mCherry reporter under the control of a Gli responsive promoter, which can be followed by using fluorescent microscopy and in situ hybridization. Expression of the mCherry transgene reporter during embryogenesis and early larval development faithfully replicated known expression domains of Hh-signaling in zebrafish, and abrogating Hh-signaling in transgenic fish resulted in the suppression of reporter expression. Moreover, ectopic shh expression in Tg(Glid:mCherry) fish led to increased transgene production. Using this transgenic line we investigated the nature of Hh-pathway response during early craniofacial development and determined that the neural crest skeletal precursors do not directly respond to Hh-signaling prior to 48 hours post fertilization, suggesting that earlier requirements for pathway activation in this population of facial skeleton precursors are indirect.We have determined that early Hh-signaling requirements in craniofacial development are indirect. We further demonstrate the Tg(Gli-d:mCherry) fish are a highly useful tool for studying Hh-signaling dependent processes during embryogenesis and larval stages
Miniature probe for mapping mechanical properties of vascular lesions using acoustic radiation force optical coherence elastography
Cardiovascular diseases are the leading cause of fatalities in the United States. Atherosclerotic plaques are one of the primary complications that can lead to strokes and heart attacks if left untreated. It is essential to diagnose the disease early and distinguish vulnerable plaques from harmless ones. Many methods focus on the structural or molecular properties of plaques. Mechanical properties have been shown to change drastically when abnormalities develop in arterial tissue. We report the development of an acoustic radiation force optical coherence elastography (ARF-OCE) system that uses an integrated miniature ultrasound and optical coherence tomography (OCT) probe to map the relative elasticity of vascular tissues. We demonstrate the capability of the miniature probe to map the biomechanical properties in phantom and human cadaver carotid arteries
Cost Effectiveness of a 21-Gene Recurrence Score Assay Versus Canadian Clinical Practice in Post-Menopausal Women with Early-Stage Estrogen or Progesterone-Receptor-Positive, Axillary Lymph-Node Positive Breast Cancer
Cost-utility of the 21-gene recurrence score assay in node-negative and node-positive breast cancer
The 21-gene recurrence score (Oncotype DX: RS) appears to augment clinico-pathologic prognostication and is predictive of adjuvant chemotherapy benefit in node-negative (N-) and node-positive (N+), endocrine-sensitive breast cancer. RS is a costly assay that is associated with good 'value for money' in N- disease, while economic evaluations in N+ disease based on most recent data have not been conducted. We examined the cost-utility (CU) of a RS-guided adjuvant strategy, compared to current practice without RS in N- and N+, endocrine-sensitive, breast cancer from a Canadian health care system perspective. A generic state-transition model was developed to compute cumulative costs and quality-adjusted life years (QALYs) over a 25-year horizon. Patient outcomes with and without chemotherapy in RS-untested cohorts and in those with low, intermediate and high RS were examined based on the reported prognostic and predictive impact of RS in N- and N+ disease. Chemotherapy utilization (current vs. RS-guided), unit costs and utilities were derived from a Nova Scotia Canadian population-based cohort, local unit costs and the literature. Costs and outcomes were discounted at 3% annually, and costs were reported in 2011 Canadian dollars (2,585 and 9,591 and $14,844 per QALY gained for N- and N+ disease, respectively. CU estimates were robust to key model parameters, and were most sensitive to chemo utilization proportions. RS-guided adjuvant therapy appears to be a cost-effective strategy in both N- and N+, endocrine-sensitive breast cancer with resultant CU ratios well below commonly quoted thresholds