Search

Chronic obstructive pulmonary disease (COPD) is increasingly being recognized as a highly heterogeneous disorder, composed of varying pathobiology. Accurate detection of COPD subtypes by image biomarkers is urgently needed to enable individualized treatment, thus improving patient outcome. We adapted the parametric response map (PRM), a voxel-wise image analysis technique, for assessing COPD phenotype. We analyzed whole-lung computed tomography (CT) scans acquired at inspiration and expiration of 194 individuals with COPD from the COPDGene study. PRM identified the extent of functional small airways disease (fSAD) and emphysema as well as provided CT-based evidence that supports the concept that fSAD precedes emphysema with increasing COPD severity. PRM is a versatile imaging biomarker capable of diagnosing disease extent and phenotype while providing detailed spatial information of disease distribution and location. PRM's ability to differentiate between specific COPD phenotypes will allow for more accurate diagnosis of individual patients, complementing standard clinical techniques., COPD is an increasingly prevalent disorder characterized by incompletely reversible airflow limitation (1), (2). Presently, it is the fourth leading cause of death in the United States, with over 11 [...]

Here we describe the parametric response map (PRM), a voxel-wise approach for image analysis and quantification of hemodynamic alterations during treatment for 44 patients with high-grade glioma. Relative cerebral blood volume (rCBV) and flow (rCBF) maps were acquired before treatment and after 1 and 3 weeks of therapy. We compared the standard approach using region-of-interest analysis for change in rCBV or rCBF to the change in perfusion parameters on the basis of PRM ([PRM.sub.rcBV] and [PRM.sub.rcBF]) for their accuracy in predicting overall survival. Neither the percentage change of rCBV or rCBF predicted survival, whereas the regional response evaluations made on the basis of PRM were highly predictive of survival. Even when accounting for baseline rCBV, which is prognostic, [PRM.sub.rcBV] proved more predictive of overall survival., Functional imaging approaches complement anatomical magnetic resonance imaging (MRI) scans and are increasingly being evaluated in oncology practice for diagnosis and assessment of treatment response (1-3). Dynamic contrast-enhanced and dynamic [...]

The serine/threonine kinase Akt mediates mitogenic and anti-apoptotic responses that result from activation of multiple signaling cascades. It is considered a key determinant of tumor aggressiveness and is a major target for anticancer drug development. Here, we describe a new reporter molecule whose bioluminescence activity within live cells and in mice can be used to measure Akt activity. Akt activity in cultured cells and tumor xenografts was monitored quantitatively and dynamically in response to activation or inhibition of receptor tyrosine kinase, inhibition of phosphoinositide 3-kinase, or direct inhibition of Akt. The results provide unique insights into the pharmacokinetics and pharmacodynamics of agents that modulate Akt activity, revealing the usefulness of this reporter for rapid dose and schedule optimization in the drug development process., Author(s): Limin Zhang [1]; Kuei C Lee [2]; Mahaveer S Bhojani [1]; Amjad P Khan [1]; Alla Shilman [1]; Eric C Holland [3]; Brian D Ross [2, 4]; Alnawaz Rehemtulla [...]

Nanoparticle-based photonic explorers have been developed for intracellular sensing and photodynamic therapy (PDT). The design employs nanoparticles made of various matrices as multifunctional nanoplatforms, loading active components by encapsulation or covalent attachment. The nanoplatform for biosensing has been successfully applied to intracellular measurements of important ionic and molecular species. The nanoplatform for PDT has shown high therapeutic efficacy in a rat 9L gliosarcoma model. Specifically, a multifunctional nanoplatform that encompasses magnetic resonance imaging (MRI) and PDT agents inside, as well as targeting ligands on the surface, has been developed and applied in vivo, resulting in much improved MRI contrast enhancement and PDT efficacy. OCIS codes: 170.0170, 170.3880.

In an effort to identify a clinical biomarker for lung cancer, we used cDNA microarray and 2D protein analyses to demonstrate that increased Fas-associated death domain (FADD) mRNA and protein were significantly associated with poor survival. Analyses of copy number and sequence of the FADD gene in 24 independent tumors ruled out the existence of an amplified and/or mutated FADD gene in aggressive lung cancers. Immunohistochemistry-based tissue microarray analysis showed that nuclear localization of FADD and elevation of the phosphorylated form of FADD (p-FADD) correlated with poor outcome (P = 0.003). Tumors with increased p-FADD expression showed elevated NF-[kappa]B (P = 0.004) activation, a frequent molecular alteration associated with tumorigenesis and metastasis in a variety of cancers. To provide a link between p-FADD and NF-[kappa]B, cell culture studies demonstrated that overexpression of p-FADD leads to an increase in NF-[kappa]B activity and a decrease in the number of cells in the G2 phase of the cell cycle, compared with cells expressing the nonphosphorylatable form of FADD or the vector control. Furthermore, cDNA microarray analyses of lung tumor samples showed that increased levels of FADD transcripts were significantly correlated with overexpression of cyclins D1 (P < 0.01) and B1 (P < 0.01), genes that are involved in the regulation of cell cycle progression and are inducible by NF-[kappa]B. These studies demonstrate that induction of NF-[kappa]B activity and its effects on cell-cycle progression may represent a molecular basis underlying the aggressive tumor behavior associated with elevated p-FADD expression in lung adenocarcinoma. survival | proliferation | lung cancer