Next-generation sequencing reveals genetic heterogeneity and resistance mechanisms in patients with -mutated non-small cell lung cancer treated with afatinib.

Background: Afatinib, an irreversible ErbB family inhibitor, is widely used as first-line treatment in advanced lung adenocarcinoma patients harbouring mutant epidermal growth factor receptor (EGFR). With the advancements in next-generation sequencing (NGS), comprehensive research into the clinical impact of co-occurring genetic mutations and the molecular mechanisms of acquired resistance is required for afatinib users.

Materials: From January 2010 to December 2019, we enrolled patients with advanced lung adenocarcinoma with mutations using afatinib as first-line treatment, and we retrospectively collected pre- and post-afatinib treatment specimens from these patients for NGS testing.

MiR-503 pleiotropically regulates epithelial-mesenchymal transition and targets PTK7 to control lung cancer metastasis.

Objective: In lung cancer patients, most deaths are caused by the distant dissemination of cancer cells. Epithelial-mesenchymal transition (EMT) and collective cell migration are distinct and important mechanisms involved in cancer invasion and metastasis. Additionally, microRNA dysregulation contributes significantly to cancer progression.

pH Dependence of a GPR4 Selective Antagonist Hampers Its Therapeutic Potential.

Inflammatory bowel disease (IBD) is characterized by chronic mucosal inflammation of the gastrointestinal tract and is associated with extracellular acidification of mucosal tissue. Several extracellular pH-sensing receptors, including G protein-coupled receptor 4 (GPR4), play an important role in the regulation of inflammatory and immune responses, and GPR4 deficiency has been shown to be protective in IBD animal models. To confirm the therapeutic potential of GPR4 antagonism in IBD, we tested Compound 13, a selective GPR4 antagonist, in the interleukin 10-/- mouse model of colitis.

Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma.

Unlabelled: The Warburg effect is the major metabolic hallmark of cancer. According to Warburg himself, the consequence of the Warburg effect is cell dedifferentiation. Therefore, reversing the Warburg effect might be an approach to restore cell differentiation in cancer.

Visualizing the interplay of Dirac mass gap and magnetism at nanoscale in intrinsic magnetic topological insulators.

In intrinsic magnetic topological insulators, Dirac surface-state gaps are prerequisites for quantum anomalous Hall and axion insulating states. Unambiguous experimental identification of these gaps has proved to be a challenge, however. Here, we use molecular beam epitaxy to grow intrinsic MnBiTe thin films.

Deep Learning Detection of Active Pulmonary Tuberculosis at Chest Radiography Matched the Clinical Performance of Radiologists.

Background The World Health Organization (WHO) recommends chest radiography to facilitate tuberculosis (TB) screening. However, chest radiograph interpretation expertise remains limited in many regions. Purpose To develop a deep learning system (DLS) to detect active pulmonary TB on chest radiographs and compare its performance to that of radiologists.

Pathogenic autoantibodies to IFN-γ act through the impedance of receptor assembly and Fc-mediated response.

Anti-interferon (IFN)-γ autoantibodies (AIGAs) are a pathogenic factor in late-onset immunodeficiency with disseminated mycobacterial and other opportunistic infections. AIGAs block IFN-γ function, but their effects on IFN-γ signaling are unknown. Using a single-cell capture method, we isolated 19 IFN-γ-reactive monoclonal antibodies (mAbs) from patients with AIGAs.

Clinicopathological Features and Survival Outcomes of Primary Pulmonary Invasive Mucinous Adenocarcinoma.

Pulmonary invasive mucinous adenocarcinoma (IMA) has unique histological patterns. This study aimed to comprehensively evaluate the clinicopathological features, prognosis, and survival outcomes of IMAs. We retrospectively identified 77 patients with pulmonary IMA and reviewed their clinical and pathological features.

A 23-gene prognostic classifier for prediction of recurrence and survival for Asian breast cancer patients.

We report a 23- gene-classifier profiled from Asian women, with the primary purpose of assessing its clinical utility towards improved risk stratification for relapse for breast cancer patients from Asian cohorts within 10 years' following mastectomy. Four hundred and twenty-two breast cancer patients underwent mastectomy and were used to train the classifier on a logistic regression model. A subset of 197 patients were chosen to be entered into the follow-up studies post mastectomy who were examined to determine the patterns of recurrence and survival analysis based on gene expression of the gene classifier, age at diagnosis, tumor stage and lymph node status, over a 5 and 10 years follow-up period.

Ramucirumab or placebo plus erlotinib in EGFR-mutated, metastatic non-small-cell lung cancer: East Asian subset of RELAY.

In the global phase III RELAY study, ramucirumab plus erlotinib (RAM + ERL) demonstrated superior progression-free survival (PFS) to placebo plus erlotinib (PL + ERL) in untreated patients with epidermal growth factor receptor (EGFR) mutation-positive metastatic non-small-cell lung cancer (NSCLC) (hazard ratio (HR) [95% CI]: 0.59 [0.46-0.

Validation of Immunohistochemistry for the Detection of V600E-Mutated Lung Adenocarcinomas.

V600E mutation, a missense mutation in exon 15 resulting in valine substitution for glutamate at position 600 within the kinase domain of BRAF oncogene, is found in a subset of lung adenocarcinoma (ADC). The usefulness of immunohistochemistry (IHC) as an alternative diagnostic tool has not been validated. Moreover, the clinical information of patients with V600E-mutated lung ADC is limited.

Endoplasmic Reticulum Protein TXNDC5 Augments Myocardial Fibrosis by Facilitating Extracellular Matrix Protein Folding and Redox-Sensitive Cardiac Fibroblast Activation.

Rationale: Cardiac fibrosis plays a critical role in the pathogenesis of heart failure. Excessive accumulation of extracellular matrix (ECM) resulting from cardiac fibrosis impairs cardiac contractile function and increases arrhythmogenicity. Current treatment options for cardiac fibrosis, however, are limited, and there is a clear need to identify novel mediators of cardiac fibrosis to facilitate the development of better therapeutics.

Cancer-Associated Mutations in Endometriosis without Cancer.

Background: Endometriosis, defined as the presence of ectopic endometrial stroma and epithelium, affects approximately 10% of reproductive-age women and can cause pelvic pain and infertility. Endometriotic lesions are considered to be benign inflammatory lesions but have cancerlike features such as local invasion and resistance to apoptosis.

Methods: We analyzed deeply infiltrating endometriotic lesions from 27 patients by means of exomewide sequencing (24 patients) or cancer-driver targeted sequencing (3 patients).

1-(2,4-Dibromophenyl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-4H-indazol-4-one: A Novel Opioid Receptor Agonist with Less Accompanying Gastrointestinal Dysfunction than Morphine.

Background: The authors investigated the pharmacology and signaling pathways of the opioid receptors modulated by compound 1, 1-(2,4-dibromophenyl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-4H-indazol-4-one.

Methods: In vitro studies of compound 1 were assessed by using a radioligand-binding assay (n = 3), a cyclic adenosine monophosphate assay (n = 3), a β-arrestin assay (n = 3), an internalization assay (n = 3), and an immunohistochemistry (n = 8). In vivo studies of compound 1 were characterized using a tail-flick test (n = 5 to 6), tail-clip test (n = 7), von Frey hair test (n = 5), and charcoal meal test (n = 5).

Treating patients with ALK-positive non-small cell lung cancer: latest evidence and management strategy.

Rearrangements in anaplastic lymphoma kinase (ALK) gene and echinoderm microtubule-associated protein-like 4 (EML4) gene were first described in a small portion of patients with non-small cell lung cancer (NSCLC) in 2007. Fluorescence in situ hybridization is used as the diagnostic test for detecting an EML4-ALK rearrangement. Crizotinib, an ALK inhibitor, is effective in treating advanced ALK-positive NSCLC, and the US Food and Drug Administration approved it for treating ALK-positive NSCLC in 2011.