Multicellular contractility contributes to the emergence of mesothelioma nodules.

Malignant pleural mesothelioma (MPM) has an overall poor prognosis and unsatisfactory treatment options. MPM nodules, protruding into the pleural cavity may have growth and spreading dynamics distinct that of other solid tumors. We demonstrate that multicellular aggregates can develop spontaneously in the majority of tested MPM cell lines when cultured at high cell density.

Longitudinal analysis of complete blood count parameters in advanced-stage lung cancer patients.

Background: Metastatic lung cancer is a debilitating disease, but with the advances in immunotherapy, therapeutic options have vastly increased. Numerous complete blood count parameters (CBC) have been described as easily accessible biomarkers that might predict response to immunotherapy. However, to date, no comprehensive study has been performed on the longitudinal changes of these parameters during cancer progression.

Proteomic analysis enables distinction of early- versus advanced-stage lung adenocarcinomas.

Background: A gel-free proteomic approach was utilized to perform in-depth tissue protein profiling of lung adenocarcinoma (ADC) and normal lung tissues from early and advanced stages of the disease. The long-term goal of this study is to generate a large-scale, label-free proteomics dataset from histologically well-classified lung ADC that can be used to increase further our understanding of disease progression and aid in identifying novel biomarkers.

Methods And Results: Cases of early-stage (I-II) and advanced-stage (III-IV) lung ADCs were selected and paired with normal lung tissues from 22 patients.

Neuroendocrine subtypes of small cell lung cancer differ in terms of immune microenvironment and checkpoint molecule distribution.

Small cell lung cancer (SCLC) has recently been subcategorized into neuroendocrine (NE)-high and NE-low subtypes showing 'immune desert' and 'immune oasis' phenotypes, respectively. Here, we aimed to characterize the tumor microenvironment according to immune checkpoints and NE subtypes in human SCLC tissue samples at the protein level. In this cross-sectional study, we included 32 primary tumors and matched lymph node (LN) metastases of resected early-stage, histologically confirmed SCLC patients, which were previously clustered into NE subtypes using NE-associated key RNA genes.

Telomerase Reverse Transcriptase Promoter Mutations Identify a Genomically Defined and Highly Aggressive Human Pleural Mesothelioma Subgroup.

Purpose: Human malignant pleural mesothelioma (MPM) is characterized by dismal prognosis. Consequently, dissection of molecular mechanisms driving malignancy is of key importance. Here we investigate whether activating mutations in the telomerase reverse transcriptase () gene promoter are present in MPM and associated with disease progression, cell immortalization, and genomic alteration patterns.

Comparative expression analysis in small cell lung carcinoma reveals neuroendocrine pattern change in primary tumor versus lymph node metastases.

Background: Recent preclinical data suggest that neuroendocrine (NE) subtype of small cell lung cancer (SCLC) has strong therapeutic relevance. NE high tumors are associated with immune desert and NE low tumors are considered to have an immune oasis phenotype. Our aim was to investigate the NE phenotypes of surgically resected SCLC tumors according to inter-tumor heterogeneity.

Next-Generation Sequencing May Discriminate Extreme Long-term versus Short-term Survival in Patients with Metastatic Small Cell Lung Cancer (SCLC).

Background: Molecular underpinnings that may prognosticate survival could increase understanding of small cell lung cancer (SCLC) tumor behavior. Here, we report the clinicopathological characteristics and biomarker profiles of short-term (ST) versus long-term (LT) survival in patients with metastatic SCLC.

Methods: Of the 876 consecutive metastatic SCLC patients receiving standard of care therapy, 44 met the definition of LT and 91 for ST, respectively.

Neutrophil-lymphocyte ratio is prognostic in early stage resected small-cell lung cancer.

Background: For selected early stage small cell lung cancer (SCLC), curative intent surgery is often performed. Previous studies, predominantly from East Asia, reported that high neutrophil to lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) correlate with poor prognosis in several types of tumors including SCLC. Our aim was to investigate the prognostic value of NLR and PLR in Caucasian patients with resected SCLC, as potential tool to select patients for multimodal treatment including surgery.

Image-Based Chemical Structure Determination.

Chemical imaging is a powerful tool for understanding the chemical composition and nature of heterogeneous samples. Recent developments in elemental, vibrational, and mass-spectrometric chemical imaging with high spatial resolution (50-200 nm) and reasonable timescale (a few hours) are capable of providing complementary chemical information about various samples. However, a single technique is insufficient to provide a comprehensive understanding of chemically complex materials.

SPAG6 and L1TD1 are transcriptionally regulated by DNA methylation in non-small cell lung cancers.

Background: DNA methylation regulates together with other epigenetic mechanisms the transcriptional activity of genes and is involved in the pathogenesis of malignant diseases including lung cancer. In non-small cell lung cancer (NSCLC) various tumor suppressor genes are already known to be tumor-specifically methylated. However, from the vast majority of a large number of genes which were identified to be tumor-specifically methylated, tumor-specific methylation was unknown so far.

Limited Tumor Tissue Drug Penetration Contributes to Primary Resistance against Angiogenesis Inhibitors.

Resistance mechanisms against antiangiogenic drugs are unclear. Here, we correlated the antitumor and antivascular properties of five different antiangiogenic receptor tyrosine kinase inhibitors (RTKIs) (motesanib, pazopanib, sorafenib, sunitinib, vatalanib) with their intratumoral distribution data obtained by matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI). In the first mouse model, only sunitinib exhibited broad-spectrum antivascular and antitumor activities by simultaneously suppressing vascular endothelial growth factor receptor-2 (VEGFR2) and desmin expression, and by increasing intratumoral hypoxia and inhibiting both tumor growth and vascularisation significantly.