La Chicha qui sert à fumer du tabac parfumé est utilisé par des millions de personnes. Il y a peu de données sur les effets du chicha sur la santé, peu de régulation et les utilisateurs pensent que la chicha n’est ni addictif ni nocif. Nous avons émis l’hypothèse que la consommation même occasionnelle de la chicha chez le sujet jeune a des conséquences sur la biologie pulmonaire. Nous avons ainsi comparé 21 sujets jeunes fumeur occasionnel de Chicha à un groupe de 19 non fumeur apparié pour le sexe et l’ethnicité. Les premières anomalies chez le fumeur de cigarette étant présent au niveau des cellules pulmonaires nous avons évalué plusieurs paramètres : (1) taux plasmatique de carboxyhemoglobine (CO), (2) Score de toux et d’expectoration; (3) fonction pulmonaire; (4) Métabolites présent dans les fluides des voies respiratoires basses (ELF); (5différences cellulaires et de transcriptome des petites voies aériennes (6) composition cellulaire des lavages broncho-alvéolaires (7) le transcriptome et (9) niveau des microparticules endothéliales circulantes. Le groupe d’étude montrait des anomalies dans tous les paramètres étudiés. Comparé au groupe contrôle les fumeurs avaient plus de toux et d’expectoration, un niveau de CO plus élevé, une diminution de la capacité de diffusion du CO , des anomalies du profil métabolique des fluides alvéolaires, une augmentation des cellules sécrétoires et intermédiaires et une diminution des cellules ciliées et basales, des anomalies du transcriptome des cellules pulmonaires et de macrophages alvéolaires et une augmentation des microparticules endothéliales.LA capacité de diffusion du monoxyde de carbone qui est un paramètre lié à l’emphysème et aux pathologies des petites voies pulmonaires était affectée par l’utilisation de la chicha. Nos précédentes études avaient montré que chez les sujets fumeurs de cigarette la réduction de la capacité de diffusion malgré une spirométrie normale était associée à un risque de développer un BPCO. Nous avons ainsi évalué le risque de développer une BPCO chez le sujet fumeur avec spirométrie normale par des scanners haute résolution comparant des groupes avec capacité de diffusion diminuée (46) et normale (59). La réduction de la capacité de diffusion était associée à un risque élevé de développer une BPCO dans les 4 ans.Par ailleurs les niveaux plasmatiques des microparticules endothéliales totales et apoptotiques était élevé dans le groupe d’étude. Dans une étude chez les sujets fumeurs de cigarette, nous avons comparé des non fumeurs (28) à des fumeurs sains (61) et des fumeurs BPCO (49) sur un an. Nous avons montré que le niveau de microparticules endothéliales apoptotiques étaient élevé en continu chez les sujets fumeurs sains et avec BPCO. Un sous groupe des fumeurs sains (17) et BPCO (18) a accepté d’arrêter de fumer. 12 mois après l’arrêt de la cigarette le niveau des microparticules endothéliales totale et apoptotique était retourné à la normale pour les fumeurs sains mais restait élevé chez les fumeurs BPCO. Ainsi le niveau élevé de ces microparticules indiquait des lésions persistantes et irréversibles des capillaires pulmonaires et pourrait servir à évaluer les fumeurs de chicha au long cours.Au total, l’utilisation occasionnelle de chicha chez le sujet jeune a des conséquence clinique et biologique pulmonaire en relation avec une diminution de la capacité de diffusion. Certaines anomalies mises en évidence dans notre étude (diminution de la capacité de diffusion, Microparticules endothéliales) pourraient prédire la survenue de maladies pulmonaires chroniques obstructives. / Waterpipe, an instrument for smoking fruit-flavored tobacco, is used by millions of people worldwide. There is limited data on the health effects of waterpipe smoking, and no regulations to its use. We hypothesized that even young, light-use waterpipe smokers have abnormalities relevant to lung health. Based on the knowledge that the first abnormalities associated with cigarette smoking are in lung cells long before there are clinical abnormalities, we compared young, light-use waterpipe smokers to nonsmokers, using a variety of lung-related parameters, including: blood carboxyhemoglobin (CO) levels; cough and sputum scores; lung function; metabolites present in lower respiratory tract epithelial lining fluid (ELF); cell differentials and transcriptome of small airway epithelium (SAE); cellular composition of ELF; transcriptome of alveolar macrophages (AM); and levels of total and apoptotic endothelial microparticles (EMPs). Light-use waterpipe smokers displayed abnormalities in all parameters assessed. Compared to nonsmokers, waterpipe smokers had more cough and sputum, higher CO levels, reduced diffusing capacity for carbon monoxide (DLCO), abnormal ELF metabolome profile, increased proportions of SAE secretory and intermediate cells, reduced proportions of SAE ciliated and basal cells, markedly abnormal SAE and AM transcriptomes, and elevated levels of total and apoptotic EMPs.DLCO, a lung function parameter linked to emphysema and small airway disease, was affected by light-use waterpipe smoking. The relevance of this comes from our studies that demonstrated, in a separate cohort of cigarette smokers with normal spirometry, that reduced DLCO predicted a high risk for developing chronic obstructive pulmonary disease (COPD), a leading cause of death worldwide. We assessed the risk for developing COPD, a clinical disorder characterized by a mixture of small airway disease and parenchymal destruction (emphysema), with a serial lung function in cigarette smokers with normal spirometry and no emphysema as assessed by HRCT, by comparing smokers with reduced DLCO vs normal DLCO. Despite having normal spirometry, cigarette smokers with reduced DLCO were at significantly higher risk for developing COPD within <4 years compared to those with normal DLCO i.e., the DLCO can be used to identify smokers at high risk for developing COPD, and could be a unique parameter in future studies to assess waterpipe smokers over time.Plasma levels of total and apoptotic EMPs, indicative of pulmonary capillary endothelial apoptosis, were elevated in light-use waterpipe smokers. The possible importance of this observation was highlighted by a parallel study, where we assessed the stability and reversibility of EMP levels in nonsmokers, healthy cigarette smokers and COPD cigarette smokers at 4 time points over a period of 1 year. The levels of total and apoptotic EMPs remained high with continuous smoking in healthy and COPD cigarette smokers. A subset of the healthy cigarette smokers and COPD cigarette smokers agreed to quit smoking. Following smoking cessation for 1 year, total and apoptotic EMP levels returned to normal nonsmoker levels in healthy cigarette smokers but remained abnormally high in COPD cigarette smokers. High levels of circulating and apoptotic EMPs are indicative of persistent and irreversible destruction of pulmonary capillaries and may be another unique parameter to assess waterpipe smokers over time.In summary, young, light-use waterpipe smokers have a number of lung clinical and biologic abnormalities compared to nonsmokers, including reduced DLCO, found to predict high risk for developing COPD in cigarette smokers, and elevated plasma levels of total and apoptotic EMPs, a marker of alveolar destruction, shown to be persistent and irreversible in COPD cigarette smokers despite smoking cessation. Together, these studies suggest that even light-use waterpipe smokers may be at risk for developing lung disease.

Lung cancer surpasses all other causes of cancer-related deaths worldwide. Gene-expression microarrays have shown that differences in the cytologically normal bronchial airway can distinguish between patients with and without lung cancer. In research reported here, we have used microRNA expression in bronchial epithelium and gene expression in nasal epithelium to advance biological understanding of the lung-cancer "field of injury" and develop new biomarkers for lung cancer diagnosis. MicroRNAs are known to mediate the airway response to tobacco smoke exposure but their role in the lung-cancer-associated field of injury was previously unknown. Microarrays can measure microRNA expression; however, they are probe-based and limited to detecting annotated microRNAs. MicroRNA sequencing, on the other hand, allows the identification of novel microRNAs that may play important biological roles. We have used microRNA sequencing to discover novel microRNAs in the bronchial epithelium. One of the predicted microRNAs, now known as miR-4423, is associated with lung cancer and airway development. This finding demonstrates for the first time a microRNA expression change associated with the lung-cancer field of injury and microRNA mediation of gene expression changes within that field. The National Lung Screening Trial showed that screening high-risk smokers using CT scans decreases lung-cancer-associated mortality. Nodules were detected in over 20% of participants; however, the overwhelming majority of screening-detected nodules were non-malignant. We therefore need biomarkers to determine which screening-detected nodules are benign and do not require further invasive testing. Given that the lung-cancer-associated field of injury extends to the bronchial epithelium, our group hypothesized that the field of injury may extend farther up in the airway. Using gene expression microarrays, we have identified a nasal epithelium gene-expression signature associated with lung cancer. Using samples from the bronchial epithelium and the nasal epithelium, we have established that there is a common lung-cancer-associated gene-expression signature throughout the airway. In addition, we have developed a nasal epithelium gene-expression biomarker for lung cancer together with a clinico-genomic classifier that includes both clinical factors and gene expression. Our data suggests that gene expression profiling in nasal epithelium might serve as a non-invasive approach for lung cancer diagnosis and screening

<div>Prostate cancer (PCa) is the second leading cause of cancer related deaths in American men. In this study, I identify two combinational therapeutics to treat PCa – the combination of enzalutamide and simvastatin, and the combination of GSK126 and metformin, both of which strongly suppress PCa cell growth in vitro and in vivo via inhibiting androgen receptor (AR), an important oncogenic driver for the PCa progression. Simvastatin leads to more AR degradation when combined with enzalutamide. For the combination of GSK126 and metformin, the interaction between enhance of zeste homolog2 (EZH2) and AR is interrupted by GSK126, re-sensitizing EZH2 to metformin. Meanwhile, GSK126 inhibits EZH2’s activity. </div><div><br></div><div>Polo-like kinase 1 (PLK1), a cell cycle regulator, is usually overexpressed in non-small-cell lung cancer (NSCLC). Here, we report that PLK1 overexpression promotes the development of Kras^G12D and Trp53^fl/fl (KP)-driven lung adenocarcinoma (LADC). KP mice harboring transgenic PLK1 (KPPI) display heavier tumor burden, poorer tumor differentiation, and lower survival than KP mice. Mechanistically, PLK1 overexpression enhances the activity of MAPK pathway, via upregulating RET expression in a kinase-dependent manner. Supporting our findings, PLK1 knockout in KP mice reduces RET gene expression, inhibits MAPK pathway activity, and strongly delays LADC development. Therefore, these data reveal that PLK1 functions as an oncogene in KP-driven LADC.</div><div> </div><div><br></div>

Lung cancer is the leading cause of cancer related deaths in the United States, with an estimated 158, 040 deaths in 2015, accounting for 27% of all cancer deaths. Recent research has identified several important molecular driver oncogenes, including epidermal growth factor receptor (EGFR). EGFR is encoded by exons 18-21, each of which harbor specific mutations within the tyrosine kinase domain. These mutations can drive cell growth, proliferation, and survival, resulting in the formation of non-small cell lung cancer. The development of EGFR tyrosine kinase inhibitors, allows the targeting of these specific mutations without the toxicity normally associated with standard chemotherapy. Unfortunately, inevitably resistance to therapy manifests, requiring a change in therapy and adding complexity to treatment decision making for clinicians and patients alike. Through a comprehensive examination of current literature, this review will establish a standard for first line, targeted treatment for specific genetic mutations within the EGFR gene, as well as address treatment options once resistance to first-line therapy inevitably develops.

Adult female guinea pigs received subcutaneous implants of diethylstilbestrol-cholestrol pellets which produced splenomegaly and increased numbers of splenic Kurloff cells. Latex spheres subsequently injected intravenously were not phagocytized by Kurloff cells within the lungs and spleen as examined with the electron microscope. This is considered as evidence that Kurloff cells are probably not phagocytic. The origin of these cells is discussed.

N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) has been shown to cause changes in cultured endothelial cells and smooth muscle function at concentrations from 5 to 25 mM. To determine whether HEPES also affects vascular permeability, the effects of two buffers, HEPES and phosphate, were compared in isolated perfused rabbit lungs. Hemodynamic parameters and vascular protein permeability-surface area products (PS) were measured after perfusion with the buffers. Endothelial permeability was measured for an anionic and a cationic albumin to assess the charge effects of the zwitterion buffer. With HEPES, there were no changes in vascular pressure or resistance but permeability was affected. Cationic albumin permeability increased with 12 mM HEPES (8.7(phosphate) → 30(12 mM HEPES) x ml · min-1 · g dry lung-1 x 10-2) as did the anionic albumin PS (2.7(phosphate) → 3.52(12 mM HEPES). The cationic PS returned to baseline (8.1(60 mM HEPES)) at 60 mM HEPES, but the anionic PS did not change from the 12 mM HEPES (4.01(60 mM HEPES)). In summary, we find that HEPES is not innocuous. Although hemodynamic parameters did not change, endothelial permeability was increased when HEPES was used at normal concentrations. Therefore, HEPES should be used with caution as a physiological buffer in perfused organ systems.

In vitro studies indicate that the inflammatory response to zymosan, a fungal wall preparation, is dependent on Toll-like receptor (TLR) 2, and that this response is enhanced by the dectin-1 receptor. Complement may also play an important role in this inflammatory response. However, the relevance of these molecules within the in vivo pulmonary environment remains unknown. To examine pulmonary in vivo inflammatory responses of the lung to zymosan, zymosan was administered by intratracheal aerosolization to C57BL/6, TLR2- TLR4-, MyD88-, and complement-deficient mice. Outcomes included bronchoalveolar fluid cell counts. We next examined effects of dectin-1 inhibition on response to zymosan in alveolar macrophages in vitro and in lungs of C57BL/6, TLR2-, and complement-deficient mice. Finally, the effect of alveolar macrophage depletion on in vivo pulmonary responses was assessed. Marked zymosan-induced neutrophil responses were unaltered in TLR2-deficient mice despite a TLR2-dependent response seen with synthetic TLR2 agonists. TLR4, MyD88, and complement activation were not required for the inflammatory response to zymosan. Although dectin-1 receptor inhibition blocked the inflammatory response of alveolar macrophages to zymosan in vitro, in vivo pulmonary leukocyte recruitment was not altered even in the absence of TLR2 or complement. Depletion of alveolar macrophages did not affect the response to zymosan. Neither complement, macrophages, nor TLR2, TLR4, MyD88, and/or dectin-1 receptors were involved in the pulmonary in vivo inflammatory response to zymosan.

Hepatitis C virus (HCV) infection is a chronic blood-borne disease that affects > 4,000,000 individuals in the United States. The majority of individuals with HVC infection acquire a chronic hepatitis that predisposes them to the complications of cirrhosis and hepatoma. Chronic HCV infection is, however, associated with multiple extrahepatic manifestations as well, including recently recognized effects on the lung. These include primary effects on lung function, as well as secondary effects in the settings of progressive liver disease and drug treatment for HCV. In this article, we discuss the emerging clinical data that support a role for HCV infection in lung disease, describe the multiple pulmonary manifestations of this viral infection, and outline the therapies available for specific pulmonary complications of chronic HCV infection.

Abstract Introduction & Background: One of the most common and debilitating side effects of cancer is fatigue. Fatigue is a general feeling of tiredness or weakness that can greatly impact a patient’s quality of life. It can have a profound impact on a patient’s ability to perform day to day activities and cause emotional distress leading to anxiety and depression. In recent years, there has been an increase in research to look at the effectiveness of non-pharmacological interventions on improving cancer patients’ fatigue. Purpose Statement: The purpose of our research is to look at the effectiveness of different types of non-pharmacological interventions on improving fatigue in lung cancer patients. Literature Review: The ETSU Library Database was used to locate the articles reviewed for this research. Only articles that were peer reviewed, open access, and available online were used. Articles that were published in 2016 or before were eliminated in the search to ensure the research’s relevancy. A total of five articles were selected to be reviewed. Findings: Progressive muscle relaxation therapy, physical therapies such as acupressure, acupuncture, and transcutaneous electrical acupoint stimulation, psychological intervention using the PERMA framework, and light exercise and balance programs consisting of walking in place showed an improvement in cancer patients’ level of fatigue. Conclusions: Non-pharmacological interventions for fatigue, compared to traditional pharmacological treatments, prove to have fewer adverse side-effects and risks for the patient. Therefore, these interventions are a safer and effective option in managing the distressing symptoms like fatigue that many lung cancer patients face while undergoing treatment.

Cis-platinum is a widely used cytotoxic agent with known radiosensitising properties. It is used in the treatment of various types of lung cancer that may include radiation to the lung as part of the treatment protocol. There is little evidence and some conflict as to whether it sensitises pulmonary tissue to the effects of radiation treatment. This project investigates the effect of cis-platinum alone or in combination with radiation on mouse lung. Four end points were used to evaluate treatments. They were: the release of pulmonary surfactant, changes in breathing rate, a histology based score of damage and changes in TGF-β - a cytokine important in the development of fibrosis. Single doses of either cis-platinum or radiation, cis-platinum given immediately before a single dose of radiation, cis-platinum given immediately before the first of two fractions of radiation and cis-platinum given at various times before and after a single dose of radiation were investigated. Cis-platinum alone was observed to cause an increase in the phospholipid content of lavaged surfactant. Cis-platinum was observed to cause an early release in surfactant and a trend existed for it to induce an early increase in breathing rates as compared to that induced by radiation alone. Cis-platinum was observed to increase radiation damage as assessed using a histology based scoring system. Higher TGF-β levels in lavaged surfactant were observed in C57 /Bl mice as compared to Balb/C. No difference in TGF-β levels was seen in homogenised lung between the strains. Cis-platinum may cause changes in TGF-β in C57/Bl mice but further work is necessary to confirm this.