The rapid development of targeted therapies has enormously changed the clinical management of lung cancer patients over the past decade; therefore, molecular testing, such as epidermal growth factor receptor (EGFR) gene mutations or anaplastic lymphoma kinase (ALK) gene rearrangements, is now routinely used to predict the therapeutic responses in lung cancer patients. Moreover, as technology and knowledge supporting molecular testing is rapidly evolving, the landscape of targetable genomic alterations in lung cancer is expanding as well. This article will summarize the current state of the most commonly altered and most clinically relevant genes in lung cancer along with a brief review of potential future developments in molecular testing of lung cancer.
The US National Lung Screening Trial (NLST) demonstrated a 20% reduction in lung cancer mortality and a 6.7% decrease in all-cause mortality. The NLST is the only trial showing positive results in a high-risk population, such as in patients with old age and heavy ever smokers. Lung cancer screening using a low-dose chest computed tomography might be beneficial for the high-risk group. However, there may also be potential adverse outcomes in terms of over diagnosis, bias and cost-effectiveness. Until now, lung cancer screening remains controversial. In this review, we wish to discuss the evolution of lung cancer screening and summarize existing evidences and recommendations.
MicroRNAs (miRNAs) are a class of small noncoding RNAs that modulate target gene activity, and are aberrantly expressed in most types of cancer as well in lung cancer. A miRNA can potentially target a diverse set of mRNAs; further, it plays a critical role in lung tumorigenesis as well as affects patient outcome. Previous studies focused mainly on abnormal miRNAs expressions in lung cancer tissues. Interestingly, circulating miRNAs were identified in human plasma and serum in 2008. Since then, considerable effort has been directed to the study of circulating miRNAs as one of the biomarkers of lung cancer. miRNAs expression of tissues and blood in lung cancer patients is being analyzed by more researchers. Recently, to overcome the high false-positivity of low-dose chest computed tomography scan, miRNAs in lung cancer screening are being investigated. This article summarizes the recent researches regarding clinical applications of miRNAs in the diagnosis and management of lung cancer.
Background: It is valuable to find the potential activity of regulating the excessive mucin secretion by the compounds derived from various medicinal plants. We investigated whether aqueous extract of the root bark of Morus alba L. (AMA), kuwanon E, kuwanon G, mulberrofuran G, and morusin significantly affect the secretion and production of airway mucin using in vivo and in vitro experimental models. Methods: Effect of AMA was examined on hypersecretion of airway mucin in sulfur dioxide-induced acute bronchitis in rats. Confluent NCI-H292 cells were pretreated with ethanolic extract, kuwanon E, kuwanon G, mulberrofuran G, or morusin for 30 minutes and then stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 hours. The MUC5AC mucin secretion and production were measured by enzyme-linked immunosorbent assay. Results: AMA stimulated the secretion of airway mucin in sulfur dioxide-induced bronchitis rat model; aqueous extract, ethanolic extract, kuwanon E, kuwanon G, mulberrofuran G and morusin inhibited the production of MUC5AC mucin induced by PMA from NCI-H292 cells, respectively. Conclusion: These results suggest that extract of the root bark and the natural products derived from Morus alba L. can regulate the secretion and production of airway mucin and, at least in part, explains the folk use of extract of Morus alba L. as mucoregulators in diverse inflammatory pulmonary diseases.
Background: Low levels of serum vitamin D is associated with several lung diseases. The production and activationof matrix metalloproteinases (MMPs) may play an important role in the pathogenesis of emphysema. The aim of thecurrent study therefore is to investigate if vitamin D modulates the expression and activation of MMP-2 and MMP-9 inhuman lung fibroblasts (HFL-1) cells. Methods: HFL-1 cells were cast into three-dimensional collagen gels and stimulated with or without interleukin-1β (IL-1β) in the presence or absence of 100 nM 25-hydroxyvitamin D (25(OH)D) or 1,25-dihydroxyvitamin D (1,25(OH)2D) for48 hours. Trypsin was then added into the culture medium in order to activate MMPs. To investigate the activity of MMP-2 and MMP-9, gelatin zymography was performed. The expression of the tissue inhibitor of metalloproteinase (TIMP-1, TIMP-2) was measured by enzyme-linked immunosorbent assay. Expression of MMP-9 mRNA and TIMP-1, TIMP-2mRNA was quantified by real time reverse transcription polymerase chain reaction. Results: IL-1β significantly stimulated MMP-9 production and mRNA expression. Trypsin converted latent MMP-2 and MMP-9 into their active forms of MMP-2 (66 kDa) and MMP-9 (82 kDa) within 24 hours. This conversion wassignificantly inhibited by 25(OH)D (100 nM) and 1,25(OH)2D (100 nM). The expression of MMP-9 mRNA was alsosignificantly inhibited by 25(OH)D and 1,25(OH)2D. Conclusion: Vitamin D, 25(OH)D, and 1,25(OH)2D play a role in regulating human lung fibroblast functions in woundrepair and tissue remodeling through not only inhibiting IL-1β stimulated MMP-9 production and conversion to its activeform but also inhibiting IL-1β inhibition on TIMP-1 and TIMP-2 production.
A patient treated with venlafaxine for major depression developed an interstitial lung disease (ILD) with the characteristic clinical, radiological and pathological features of chronic hypersensitivity pneumonitis. A high resolution computed tomography scan demonstrated ground glass opacity, mosaic perfusion with air-trapping and traction bronchiectasis in both lungs. The pathological findings were consistent with a nonspecific interstitial pneumonia pattern. Clinical and radiological improvements were noted after the discontinuation of venlafaxine and the administration of a corticosteroid. This report provides further evidence that the anti-depressant venlafaxine can cause ILD.
Intrathoracic involvement of immunoglobulin G4 (IgG4)-related disease has recently been reported. However, a subset of the disease presenting as interstitial lung disease is rare. Here, we report a case of a 35-year-old man with IgG4-related lung disease with manifestations similar to those of interstitial lung disease. Chest computed tomography showed diffuse ground glass opacities and rapidly progressive pleural and subpleural fibrosis in both upper lobes. Histological findings showed diffuse interstitial lymphoplasmacytic infiltration with an increased number of IgG4-positive plasma cells. Serum levels of IgG and IgG4 were also increased. The patient was diagnosed with IgG4-related lung disease, treated with anti-inflammatory agents, and showed improvement. Lung involvement of IgG4-related disease can present as interstitial lung disease and, therefore, should be differentiated when evaluating interstitial lung disease.
Hyaluronic acid is widely used in medical procedures, particularly in cosmetic procedures administered by physicians or nonmedical personnel. The materials used for cosmetic procedures by physicians as well as illegally by non-medical personnel can cause nonthrombotic pulmonary embolism (NTPE). We report the case of a woman with acute respiratory failure, neurologic symptoms and petechiae after an illegal procedure of hyaluronic acid dermal filler performed by an unlicensed medical practitioner 3 days before symptom onset. Although a few cases of NTPE after injection of hyaluronic acid have been reported yet, this is the first typical case showing a NTPE manifestation after the facial injection of hyaluronic acid.
Empyema necessitatis is a rare complication of an empyema. Although the incidence is thought to be decreased in the post-antibiotic era, immunocompromised patients such as patients with chronic kidney disease on dialysis are still at a higher risk. A 56-year-old woman on peritoneal dialysis presented with an enlarging mass on the right anterior chest wall. The chest computed tomography scan revealed an empyema necessitatis and the histopathologic findings revealed a granulomatous inflammation with caseation necrosis. The patient was treated with anti-tuberculous medication.