Lung cacer

Supergenes are involved in adaptation in multiple organisms, but they are little known in humans. Genomic inversions are the most common mechanism of supergene generation and maintenance. Here, we review the information about two large inversions that are the best examples of potential human supergenes. In addition, we do an integrative analysis of the newest data to understand better their functional effects and underlying genetic changes. We have found that the highly divergent haplotypes of the 17q21.31 inversion of approximately 1...

A 34-year-old man presented to our institution with lightheadedness and dyspnea on exertion. His medical history included chronic pancreatitis, juvenile rheumatoid arthritis (JRA), gastroesophageal reflux disease, hypertension, lumbar degenerative disc disease, seizure disorder, anterior uveitis, and multiple vertebral fractures. In addition, he was a cigarette smoker with a 10-pack-year smoking history.

Two mycobacteriophages were administered intravenously to a male with treatment-refractory Mycobacterium abscessus pulmonary infection and severe cystic fibrosis lung disease. The phages were engineered to enhance their capacity to lyse M. abscessus and were selected specifically as the most effective against the subject's bacterial isolate. In the setting of compassionate use, the evidence of phage-induced lysis was observed using molecular and metabolic assays combined with clinical assessments. M. abscessus isolates pre and post-phage treatment demonstrated genetic stability, with a general decline in diversity and no increased resistance to phage or antibiotics...

Background: It is imperative to identify drugs that allow treating symptoms of severe COVID-19. Respiratory failure is the main cause of death in severe COVID-19 patients, and the host inflammatory response at the lungs remains poorly understood. Methods: Therefore, we retrieved data from post-mortem lungs from COVID-19 patients and performed in-depth in silico analyses of single-nucleus RNA sequencing data, inflammatory protein interactome network, and shortest pathways to physiological phenotypes to reveal potential therapeutic targets and drugs in advanced-stage COVID-19 clinical trials...

BACKGROUND: ALK rearrangements are present in 5% of nonsmall cell lung cancer (NSCLC) tumors and identify patients who can benefit from ALK inhibitors. ALK fusions testing using liquid biopsies, although challenging, can expand the therapeutic options for ALK-positive NSCLC patients considerably. RNA inside extracellular vesicles (EVs) is protected from RNases and other environmental factors, constituting a promising source for noninvasive fusion transcript detection. METHODS: EVs from H3122 and H2228 cell lines, harboring EML4-ALK variant 1 (E13; A20) and variant 3 (E6a/b; A20), respectively, were successfully isolated by sequential centrifugation of cell culture supernatants...

BACKGROUND: Extracellular vesicles (EVs), released by most cell types, provide an excellent source of biomarkers in biological fluids. However, in order to perform validation studies and screenings of patient samples, it is still necessary to develop general techniques permitting rapid handling of small amounts of biological samples from large numbers of donors. RESULTS: Here we describe a method that, using just a few microliters of patient's plasma, identifies tumour markers exposed on EVs...

Air pollution exposure positively correlates with increased cardiovascular morbidity and mortality rates, mainly due to myocardial infarction (MI). Herein, we aimed to study the metabolic mechanisms underlying this association, focusing on the evaluation of cardiac mitochondrial function and dynamics, together with its impact over MI progression. An initial time course study was performed in BALB/c mice breathing filtered air (FA) or urban air (UA) in whole-body exposure chambers located in Buenos Aires City downtown for up to 16 weeks (n = 8 per group and time point)...

There is an increasing concern over the harmful effects that metallic nanoparticles (NP) may produce on human health. Due to their redox properties, nickel (Ni) and Ni-containing NP are particularly relevant. Hence, the aim of this study was to establish the toxicological mechanisms in the cardiorespiratory oxidative metabolism initiated by an acute exposure to Ni-doped-NP. Mice were intranasally instilled with silica NP containing Ni (II) (Ni-NP) (1 mg Ni (II)/kg body weight) or empty NP as control, and 1 h after exposure lung, plasma, and heart samples were obtained to assess the redox metabolism...

INTRODUCTION: Racotumomab is a therapeutic vaccine based on a monoclonal anti-idiotypic antibody developed by the Molecular Immunology Center in Havana, Cuba, that is registered in Cuba and Argentina for treatment of non-small cell lung cancer. It induces a specific humoral and cellular immune response against the N-glycolyl GM3 (NeuGcGM3) ganglioside present in tumor cells, thereby provoking the death of these cells. OBJECTIVE: Evaluate racotumomab vaccine use as switch maintenance and second-line therapy for patients with inoperable non-small cell lung cancer in routine clinical practice, outside the framework of clinical studies, and assess the overall survival, stage-specific survival and safety in these patients...

Despite many advancements in recent years for the sampling of peripheral pulmonary lesions, the diagnostic yield remains low. Initial excitement about the current electromagnetic navigation platforms has subsided as the real-world data shows a significantly lower diagnostic sensitivity of ~70%. "CT-to-body divergence" has been identified as a major limitation of this modality. In-tandem use of the ultrathin bronchoscope and radial endobronchial ultrasound probe has yielded only comparable results, attributable to the limited peripheral reach, device maneuverability, stability, and distractors like atelectasis...

BACKGROUND: Clinically evident interstitial lung disease (ILD) affects between 10 and 42% of the patients with rheumatoid arthritis (RA). Airway involvement seems to be even more common. Most of the available evidence comes from studies performed in established RA patients. The aim of our study was to know the prevalence of non-diagnosed lung disease (airway and interstitial involvement) in patients with early RA and look for associated factors. METHODS: We designed an observational, multicenter, cross-sectional study, and included patients with RA of less than two years since diagnosis...

Transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in millions of deaths and declining economies around the world. K18-hACE2 mice develop disease resembling severe SARS-CoV-2 infection in a virus dose-dependent manner. The relationship between SARS-CoV-2 and the intestinal or respiratory microbiome is not fully understood. In this context, we characterized the cecal and lung microbiomes of SARS-CoV-2-challenged K18-hACE2 transgenic mice in the presence or absence of treatment with the Mpro inhibitor GC-376...

About 4% to 7% of the non-small-cell lung cancer patients have anaplastic lymphoma kinase (ALK) rearrangements, and specific targeted therapies improve patients' outcomes significantly. ALK gene fusions are detected by immunohistochemistry or fluorescent in situ hybridization as gold standards in South America. Next-generation sequencing-based assays are a reliable alternative, able to perform simultaneous detection of multiple events from a single sample. We analyzed 4240 non-small-cell lung cancer samples collected in 37 hospitals from Chile, Brazil, and Peru, where ALK rearrangements were determined as part of their standard of care (SofC) using either immunohistochemistry or fluorescent in situ hybridization...

Background: There is pressing urgency to identify therapeutic targets and drugs that allow treating COVID-19 patients effectively. Methods: We performed in silico analyses of immune system protein interactome network, single-cell RNA sequencing of human tissues, and artificial neural networks to reveal potential therapeutic targets for drug repurposing against COVID-19. Results: We screened 1,584 high-confidence immune system proteins in ACE2 and TMPRSS2 co-expressing cells, finding 25 potential therapeutic targets significantly overexpressed in nasal goblet secretory cells, lung type II pneumocytes, and ileal absorptive enterocytes of patients with several immunopathologies...

Identifying the druggable target is crucial for patients with nonsquamous advanced non-small cell lung cancer (NSCLC). This article adds to the spectrum of ROS1 fusion cases described in NSCLC. We describe a novel SLC12A2-ROS1 rearrangement that has not been previously reported in other cancers: a fusion that has clinical and radiological sensitivity to crizotinib. Fluorescence in situ hybridization detected the SLC12A2-ROS1 fusion and it was confirmed through hybrid capture-based next-generation sequencing (NGS); however, the fusion could not be detected by amplicon-based assay...

The underlying mechanisms contributing to injury-induced infection susceptibility remain poorly understood. Here, we describe a rapid increase in neutrophil cell numbers in the lungs following induction of thermal injury. These neutrophils expressed elevated levels of programmed death ligand 1 (PD-L1) and exhibited altered gene expression profiles indicative of a reparative population. Upon injury, neutrophils migrate from the bone marrow to the skin but transiently arrest in the lung vasculature. Arrested neutrophils interact with programmed cell death protein 1 (PD-1) on lung endothelial cells...

On a global scale, cetaceans are recognized well indicators of marine ecosystem health. Trace elements accumulate in their bodies and potentially constitute a toxicological threat. Here, the concentrations of essential Se; unknown physiological elements Br, Rb, Cs, Ni, and Sr; and pollutants arsenic, Cd, Hg, and Ag were assessed in the skin of false killer whales (Pseudorca crassidens) stranded at Estrecho de Magallanes, South America, and next, tissue comparisons and relationships between elemental concentrations in the skin and internal tissues (liver, kidney, spleen, lung, skeletal muscle, and testis) were assessed...

Along with the AgNP applications development, the concern about their possible toxicity has increasingly gained attention. As the respiratory system is one of the main exposure routes, the aim of this study was to evaluate the harmful effects developed in the lung after an acute AgNP exposure. In vivo studies using Balb/c mice intranasally instilled with 0.1 mg AgNP/kg b.w, were performed. 99m Tc-AgNP showed the lung as the main organ of deposition, where, in turn, AgNP may exert barrier injury observed by increased protein content and total cell count in BAL samples...

PURPOSE OF REVIEW: To review and compare the constellations of causes and consequences of the two current pandemics, Covid-19 and climate change. RECENT FINDINGS: There has been a transient counterbalancing, in which the response to Covid-19 has briefly mitigated pollution and greenhouse gasses. This divergence belies multiple commonalities of cause and effect. SUMMARY: The convergence of these two pandemics is unprecedented. Although at first glance, they appear to be completely unrelated, they share striking commonalities...

Cervical cancer (CC) continues to be one of the leading causes of death for women across the world. Although it has been determined that papillomavirus infection is one of the main causes of the etiology of the disease, genetic and epigenetic factors are also required for its progression. Among the epigenetic factors are included the long noncoding RNAs (lncRNAs), transcripts of more than 200 nucleotides (nt) that generally do not code for proteins and have been associated with diverse functions such as the regulation of transcription, translation, RNA metabolism, as well as stem cell maintenance and differentiation, cell autophagy and apoptosis...