Transcription factor c-Maf is a checkpoint that programs macrophages in lung cancer.

Macrophages have been linked to tumor initiation, progression, metastasis, and treatment resistance. However, the transcriptional regulation of macrophages driving the protumor function remains elusive. Here, we demonstrate that the transcription factor c-Maf is a critical controller for immunosuppressive macrophage polarization and function in cancer.

Metabolic reprogramming and Notch activity distinguish between non-small cell lung cancer subtypes.

Background: Previous studies suggested that the metabolism is differently reprogrammed in the major subtypes of non-small cell lung cancer (NSCLC), squamous cell carcinomas (SCC) and adenocarcinomas (AdC). However, a comprehensive analysis of this differential metabolic reprogramming is lacking.

Methods: Publicly available gene expression data from human lung cancer samples and cell lines were analysed.

Single Versus Double Lung Retransplantation Does Not Affect Survival Based on Previous Transplant Type.

Background: Survival following retransplantation with a single lung is worse than after double lung transplant. We sought to characterize survival of patients who underwent lung retransplantation based on the type of their initial transplant, single or double.

Methods: The United Network for Organ Sharing database was queried for adult patients who underwent lung retransplantation from 2005 onward.

Normalization of Exhaled Carbonyl Compounds After Lung Cancer Resection.

Background: Quantitative analysis of specific exhaled carbonyl compounds (ECCs) has shown promise for the detection of lung cancer. The purpose of this study is to demonstrate the normalization of ECCs in patients after lung cancer resection.

Methods: Patients from a single center gave consent and were enrolled in the study from 2011 onward.

Yeast-Derived Particulate β-Glucan Treatment Subverts the Suppression of Myeloid-Derived Suppressor Cells (MDSC) by Inducing Polymorphonuclear MDSC Apoptosis and Monocytic MDSC Differentiation to APC in Cancer.

Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells that promote tumor progression. In this study, we demonstrated that activation of a C-type lectin receptor, dectin-1, in MDSC differentially modulates the function of different MDSC subsets. Yeast-derived whole β-glucan particles (WGP; a ligand to engage and activate dectin-1, oral treatment in vivo) significantly decreased tumor weight and splenomegaly in tumor-bearing mice with reduced accumulation of polymorphonuclear MDSC but not monocytic MDSC (M-MDSC), and decreased polymorphonuclear MDSC suppression in vitro through the induction of respiratory burst and apoptosis.

Dectin-1 Activation by a Natural Product β-Glucan Converts Immunosuppressive Macrophages into an M1-like Phenotype.

Tumor-associated macrophages (TAM) with an alternatively activated phenotype have been linked to tumor-elicited inflammation, immunosuppression, and resistance to chemotherapies in cancer, thus representing an attractive target for an effective cancer immunotherapy. In this study, we demonstrate that particulate yeast-derived β-glucan, a natural polysaccharide compound, converts polarized alternatively activated macrophages or immunosuppressive TAM into a classically activated phenotype with potent immunostimulating activity. This process is associated with macrophage metabolic reprograming with enhanced glycolysis, Krebs cycle, and glutamine utilization.

High sensitivity for lung cancer detection using analysis of exhaled carbonyl compounds.

Objective: Several volatile carbonyl compounds in exhaled breath have been identified as cancer-specific markers. The potential for these markers to serve as a screening test for lung cancer is reported.

Methods: Patients with computed tomography-detected intrathoracic lesions and healthy control participants were enrolled from 2011 onward.

Breath carbonyl compounds as biomarkers of lung cancer.

Objective: Lung cancer dysregulations impart oxidative stress which results in important metabolic products in the form of volatile organic compounds (VOCs) in exhaled breath. The objective of this work is to use statistical classification models to determine specific carbonyl VOCs in exhaled breath as biomarkers for detection of lung cancer.

Materials And Methods: Exhaled breath samples from 85 patients with untreated lung cancer, 34 patients with benign pulmonary nodules and 85 healthy controls were collected.

Human polymorphonuclear neutrophils specifically recognize and kill cancerous cells.

Polymorphonuclear neutrophils (PMNs), the main effectors of the innate immune system, have rarely been considered as an anticancer therapeutic tool. However, recent investigations using animal models and preliminary clinical studies have highlighted the potential antitumor efficacy of PMNs. In the current study, we find that PMNs from some healthy donors naturally have potent cancer-killing activity against 4 different human cancer cell lines.

Pyruvate carboxylase is critical for non-small-cell lung cancer proliferation.

Anabolic biosynthesis requires precursors supplied by the Krebs cycle, which in turn requires anaplerosis to replenish precursor intermediates. The major anaplerotic sources are pyruvate and glutamine, which require the activity of pyruvate carboxylase (PC) and glutaminase 1 (GLS1), respectively. Due to their rapid proliferation, cancer cells have increased anabolic and energy demands; however, different cancer cell types exhibit differential requirements for PC- and GLS-mediated pathways for anaplerosis and cell proliferation.

Quantitative analysis of exhaled carbonyl compounds distinguishes benign from malignant pulmonary disease.

Objectives: The analysis of exhaled breath is a promising noninvasive tool for the diagnosis of lung cancer, but its clinical relevance has yet to be established. We report the analysis of exhaled volatile carbonyl compounds for the identification of specific carbonyl cancer markers to differentiate benign pulmonary disease from early-stage lung cancer and to compare its diagnostic accuracy with positron emission tomography (PET) scans.

Methods: Aminooxy-coated silicon microchips were used for the selective capture of exhaled carbonyls by an oximation reaction.

Double lung transplants have significantly improved survival compared with single lung transplants in high lung allocation score patients.

Background: Historically, double lung transplantation survival rates are higher than those of single lung transplantation, but in critically ill patients a single lung transplant, with less associated operative morbidity, could afford a better outcome. This article evaluates how survival is affected in patients who have a high lung allocation score (LAS) and receive a single versus a double lung transplant.

Methods: The UNOS Thoracic Transplant Database for lung transplants from January 2005 to June 2012 was used for analysis.

Targeting lactate dehydrogenase--a inhibits tumorigenesis and tumor progression in mouse models of lung cancer and impacts tumor-initiating cells.

The lactate dehydrogenase-A (LDH-A) enzyme catalyzes the interconversion of pyruvate and lactate, is upregulated in human cancers, and is associated with aggressive tumor outcomes. Here we use an inducible murine model and demonstrate that inactivation of LDH-A in mouse models of NSCLC driven by oncogenic K-RAS or EGFR leads to decreased tumorigenesis and disease regression in established tumors. We also show that abrogation of LDH-A results in reprogramming of pyruvate metabolism, with decreased lactic fermentation in vitro, in vivo, and ex vivo.

Noninvasive detection of lung cancer using exhaled breath.

Early detection of lung cancer is a key factor for increasing the survival rates of lung cancer patients. The analysis of exhaled breath is promising as a noninvasive diagnostic tool for diagnosis of lung cancer. We demonstrate the quantitative analysis of carbonyl volatile organic compounds (VOCs) and identification of lung cancer VOC markers in exhaled breath using unique silicon microreactor technology.

Surgical management of pulmonary carcinoid tumors: sublobar resection versus lobectomy.

Background: Surgical resection of bronchopulmonary carcinoid tumors can be curative and remains the primary treatment modality. There are limited data to delineate the optimal extent of resection for this disease.

Methods: A retrospective review of the 3,270 patients diagnosed with typical and atypical carcinoid tumors between 2000 and 2007 in the Surveillance Epidemiology and End Results registry was performed.

Stable isotope-resolved metabolomics (SIRM) in cancer research with clinical application to nonsmall cell lung cancer.

Metabolomics provides a readout of the state of metabolism in cells or tissue and their responses to external perturbations. For this reason, the approach has great potential in clinical diagnostics. Clinical metabolomics using stable isotope resolved metabolomics (SIRM) for pathway tracing represents an important new approach to obtaining metabolic parameters in human cancer subjects in situ.

Effects of a localized high-flow anastomosis between the aorta and left lower lobe pulmonary artery on great vessel flow and pulmonary arterial reactivity in the contralateral lung.

Objectives: We sought to assess the effects of a localized anastomosis between the aorta and left lower lobe pulmonary artery on flows through central vessels and on the vascular reactivity of small pulmonary arteries distal or contralateral to the shunt.

Methods: Flow rates in major vessels and tensions from small pulmonary arteries from the left and right lower lobes were determined 48 hours after creation of an end-to-side anastomosis of the left lower lobe pulmonary artery to the aorta.

Results: Anastomoses increased flow through the left lower lobe pulmonary artery from 194±6 to 452±18 mL/min immediately after anastomosis to 756±19 mL/min by the time of harvest (n=88, P<.

Altered regulation of metabolic pathways in human lung cancer discerned by (13)C stable isotope-resolved metabolomics (SIRM).

Background: Metabolic perturbations arising from malignant transformation have not been systematically characterized in human lung cancers in situ. Stable isotope resolved metabolomic analysis (SIRM) enables functional analysis of gene dysregulations in lung cancer. To this purpose, metabolic changes were investigated by infusing uniformly labeled 13C-glucose into human lung cancer patients, followed by resection and processing of paired non-cancerous lung and non small cell carcinoma tissues.

Prospects for clinical cancer metabolomics using stable isotope tracers.

Metabolomics provides a readout of the state of metabolism in cells or tissue and their responses to external perturbations. For this reason, the approach has great potential in clinical diagnostics. For more than two decades, we have been using stable isotope tracer approaches to probe cellular metabolism in greater detail.

Metabolic profiling identifies lung tumor responsiveness to erlotinib.

A subtype of non-small cell lung cancer, bronchioalveolar adenocarcinoma (BAC), is more prevalent in Asian female non-smokers, and is more likely to respond to treatment with tyrosine kinase inhibitors such as erlotinib and gefitinib. Nuclear magnetic resonance and mass spectrometry-based metabolomic analysis of extracts from two different lung lesions and surrounding non-cancerous tissues of a BAC patient showed novel protein and phospholipid-associated metabolic differences that correlated with tumor development as well as PET and erlotinib sensitivity.

Late superior vena cava perforation and aortic laceration after stenting to treat superior vena cava syndrome secondary to fibrosing mediastinitis.

We describe a case of late perforation of the superior vena cava and laceration of the ascending aorta after stent implantation for superior vena cava syndrome. The etiology of the late perforation is unclear, and could be secondary to either flaring of the trailing edge of the stent or chest trauma.

Hemoptysis resulting from unilateral pulmonary artery agenesis.

Unilateral pulmonary artery agenesis is a rare congenital anomaly often associated with other cardiovascular abnormalities. It is usually diagnosed and surgically treated in childhood. Subjects without associated cardiac anomalies (isolated unilateral pulmonary artery agenesis) may be asymptomatic or have recurrent respiratory infections.