Purpose: Whole-brain radiation therapy (WBRT) has been applied to inoperable brain metastases in lung adenocarcinoma. Recently, an in vitro study showed reduced clonogenic survival of mutant epidermal growth factor receptor (EGFR) lung cancer cell lines in response to ionizing radiation compared with that of the wild type. To elucidate the role of EGFR mutations in radiation treatment, we evaluated the clinical response to WBRT and survival of lung adenocarcinoma patients with brain metastases. Experimental Design: This was a retrospective analysis of 63 patients with brain metastases from lung adenocarcinoma who were treated with WBRT. Demographic data, EGFR mutation status, response to WBRT, and survival data were collected. Clinical response was assessed 1 month after the start of WBRT. Univariate and logistic regression models were used to test potential predictive factors associated with clinical response. Log-rank test and Cox regression were analyzed to identify factors that affected survival. Results: Clinical response to WBRT was observed in 29 patients (46%), with 34 nonresponder patients (54%). Patients with EGFR mutations had higher response rates toWBRTcompared with those with the wild-type (54% versus 24%; P = 0.045). Both the administration of EGFR tyrosine kinase inhibitor (P = 0.034) and EGFR mutation (P = 0.029) were independently associated with response to WBRT. In Cox regression analysis, WBRT responder (P = 0.010) and absence of extracranial metastases (P = 0.002) were associated with better survival. Conclusions: Both the EGFR mutations and the administration of EGFR TKI during WBRT were independent predictors of response to WBRT in brain metastases of lung adenocarcinoma.

The American Society of Clinical Oncology released its first Guidance Statement on Cost of Cancer Care in August 2009, affirming patient-physician cost communication was a critical component of high-quality care. This forward-thinking recommendation has grown increasingly important in oncology practice today as the high costs of cancer care impose tremendous financial burden to patients, their families, and the healthcare system. In this review article, we conducted a literature search using Pubmed and Web of Science to identify articles covering three topics related to patient-physician cost communication: patient attitude, physician acceptance, and the associated outcomes. We identified fifteen papers from twelve distinct studies. While the majority of articles we reviewed on patient attitude suggested cost communication is desired by more than half of patients in the respective study cohorts, less than one-third of patients in these studies had actually discussed costs with their physicians. The literature on physician acceptance indicated that while 75% of physicians considered discussing out-of-pocket costs with patients their responsibility, less than 30% felt comfortable with such communication. When asked about whether cost communication actually took place in their practice, percentages reported by physicians varied widely, ranging from < 10% to > 60%. The data suggested that cost communication was associated with improved patient satisfaction, lower out-of-pocket expenses and a higher likelihood of medication non-adherence; none of these studies established causality. Both patients and physicians expressed a strong need for accurate, accessible, and transparent cost information.

This study aimed to estimate the mean sojourn time (MST) and sensitivity of asymptomatic lung cancer (ALC) detected by computed tomography (CT) or chest X-ray (CXR). Translation of early diagnosis into mortality reduction by 2 detection modalities and inter-screening interval was projected using a Markov model. On the basis of systematic literature review, data from 6 prospective CT screening studies were retrieved. The MST in association with the natural history of lung cancer depicted by a 3-state Markov model was estimated with a Bayesian approach. To project mortality reduction attributed to screening, the model was further extended to 5 health states for the inclusion of prognostic part. The analysis was run with a 10-year time horizon of follow-up, mimicking the Dutch-Belgian randomized lung cancer screening trial (NELSON). Screening for lung cancer with CT had high sensitivity (median: 97%) and may advance 1 year earlier than CXR in detecting ALC. By simulating the scenario similar to NELSON study, CT screen may gain an extra of 0.019 year of life expectancy per person, yields 15% mortality reduction (relative risk (RR): 0.85, 95% confidence interval [95%CI: (0.58-1.01)]. Approximate 23% [RR: 0.77, 95%CI: (0.43-0.98)] mortality reduction would be achieved by annual CT screening program. The mortality findings in conjunction with higher sensitivity and shorter MST estimate given data on prevalent and incident (2nd) screen may provide a tentative evidence, suggesting that annual CT screening may be required in order to be effective in reducing mortality before the results of randomized controlled studies available.

No abstract

Toward multiplexed, comprehensive, and robust quantitation of the membrane proteome, we report a strategy combining gel-assisted digestion, iTRAQ (isobaric tags for relative and absolute quantitation) labeling, and LC-MS/MS. Quantitation of four independently purified membrane fractions from HeLa cells gave high accuracy (<8% error) and precision (<12% relative S.D.), demonstrating a high degree of consistency and reproducibility of this quantitation platform. Under stringent identification criteria (false discovery rate ‫؍‬ 0%), the strategy efficiently quantified membrane proteins; as many as 520 proteins (91%) were membrane proteins, each quantified based on an average of 14.1 peptides per integral membrane protein. In addition to significant improvements in signal intensity for most quantified proteins, most remarkably, topological analysis revealed that the biggest improvement was achieved in detection of transmembrane peptides from integral membrane proteins with up to 19 transmembrane helices. To the best of our knowledge, this level of coverage exceeds that achieved previously using MS and provides superior quantitation accuracy compared with other methods. We applied this approach to the first proteomics delineation of phenotypic expression in a mouse model of autosomal dominant polycystic kidney disease (ADPKD). By characterizing kidney cell plasma membrane from wild-type versus PKD1 knock-out mice, 791 proteins were quantified, and 67 and 37 proteins showed >2-fold up-regulation and down-regulation, respectively. Some of these differentially expressed membrane proteins are involved in the mechanisms underlying major abnormalities in ADPKD, including epithelial cell proliferation and apoptosis, cell-cell and cell-matrix interactions, ion and fluid secretion, and membrane protein polarity. Among these proteins, targeting therapeutics to certain transporters/receptors, such as epidermal growth factor receptor, has proven effective in preclinical studies of ADPKD; others are known drug targets in various diseases. Our method demonstrates how comparative membrane proteomics can provide insight into the molecular mechanisms underlying ADPKD and the identification of potential drug targets, which may lead to new therapeutic opportunities to prevent or retard the disease.

No abstract

Chemokines orchestrate leukocyte migration toward sites of inflammation and infection and target leukocytes via chemokine receptors such as CCR6, a subfamily of the seven-transmembrane G-protein-coupled receptors. Lipid rafts are cholesterol and sphingolipid-enriched liquid-ordered membrane microdomains thought to serve as scaffolding platforms for signal transduction. To globally understand the dynamic changes of proteins within lipid rafts upon CCR6 activation in T cells, we quantitatively analyzed the time-dependent changes of lipid raft proteome using our recently reported membrane proteomics strategy combining gel-assisted digestion, iTRAQ labeling and LC-MS/MS. To our knowledge, the error-free identification of 852 proteins represents the first data set of the raft proteome in T cells upon chemokine receptor activation, including 354 previously annotated raft proteins and 85 dynamically recruited proteins that are potential raft-associated proteins. The temporal profiles revealed that many proteins involved in the actin cytoskeleton rearrangement are actively recruited into lipid rafts upon CCR6 activation. We further confirmed the proteomics results by Western blotting and used small interfering RNA-mediated knockdown to evaluate their roles upon CCR6 activation. In sum, we employed quantitative proteomic strategy to analyze raft proteome and identified many molecules actively involved in the control of actin assembly and disassembly regulating CCR6 activation-induced cell migration.

Whole-body FDG-PET and PET/CT are valuable imaging tools for the assessment of patients with suspected CRC tumor recurrence based on the increase of CEA.