Lance Liotta

An interventional magnetic resonance imaging technique for the molecular characterization of intraprostatic dynamic contrast enhancement.

The biological characterization of an individual patients tumor by noninvasive imaging will have an important role in cancer care and clinical research if the molecular processes that underlie the image data are known. Spatial heterogeneity in the dynamics of magnetic resonance imaging contrast enhancement (DCE-MRI) is hypothesized to reflect variations in tumor angiogenesis. Here we demonstrate the feasibility of precisely colocalizing DCE-MRI data with the genomic and proteomic profiles of underlying biopsy tissue using a novel MRI-guided biopsy technique in patients with prostate cancer.

Genomic and Proteomic Pathway Mapping Reveals Signatures of Mesenchymal-Epithelial Plasticity in Inflammatory Breast Cancer

1.1 Inflammatory breast cancer as a distinct clinicopathologic entity There are several clinically distinct types of breast cancer, which include early stage breast cancer, locally advanced breast cancer (LABC) and metastatic breast cancer. The most rare but lethal form of LABC is inflammatory breast cancer (IBC) (reviewed in 1). This type of breast cancer accounts for an estimated 25% of all breast cancers in the United States and up to 20% of all breast cancers globally (2-4). Although primary IBC is less commonly diagnosed than other types of breast cancer, IBC is responsible for a disproportionate number of breast cancer-related deaths that occur each year world-wide due to its propensity to rapidly metastasize. (2-4). Women diagnosed with IBC have a significantly shorter median survival time (~ 2.9 years) than women with either LABC (~ 6.4 years) or non-LABC breast cancer (>10 years). The clinical diagnosis of IBC is based on the combination of the physical appearance of the affected breast, a careful medical history, physical examination, and pathological findings from a skin biopsy and/or needle or core

Development and Implementation of Array Technologies for Proteomics: Clinical Implications and Applications

Array-based technologies, providing “-omic” level understanding of tumors at the DNA, RNA, and protein levels, have led to the uncovering of new disease susceptibility genes, therapeutic targets, expression profiles of genes or proteins related to disease outcomes as well as markers of therapeutic sensitivity and resistance. Analysis of signaling network activation at the protein level is of critical importance because nearly all current molecular-targeted therapeutics directed at modulating protein kinase activity, hence, the proteins themselves are the drug targets. Newer array-based and multiplexed approaches that can measure signaling network activation in very small tissue samples of the patient, and can perform broad-scale pathway mapping, will be the best to deliver effectively the needed predictive, prognostic, and therapy-guiding information to the bedside. The power of protein microarrays lies in their ability to provide a “map” of known cellular signaling proteins that generally reflect the state of information flow through protein networks in individual specimens. Combined with continued efforts to identify and monitor protein markers indicative of therapeutic response or resistance, protein array-based technologies are uniquely poised to provide direct functional information for individual patient tumors in time frames which was never before possible and could have a tremendous positive impact on therapeutic decision-making and ultimately on disease outcome.

Chapter 34 – Laser Capture Microdissection

Publisher Summary Laser capture microdissection (LCM) is a technology for procuring pure cell populations from a heterogeneous tissue or cytological preparation under direct microscopic visualization. One of the most common problems encountered by the investigator involved in the proteomic or genetic analysis of tissue samples arises from the heterogeneous nature of the tissue and the need for a pure cell population for studies. LCM enables the investigator to isolate single cells or multiple cells, representing specific malignant, premalignant, or normal tissues. The ability to analyze pure cell populations permits analysis of molecular events representative of the tissue at the time of sample procurement. The AutoPix makes it possible for the operator to conduct hands off microdissection once the relevant cells are marked by the operator or are recognized by the computer image recognition software. When using the 30-μm laser spot size, the operator can expect to collect on average five to six cells per laser pulse.