Sensitive methods for screening of the MEK1 gene mutations in patients with central nervous system metastases of non-small cell lung cancer

Background: The mitogen-activated protein kinases 1 and 2 (MEK1, MEK2) are fundamental partners in the RAS-RAF-MEK-ERK pathway that is involved in regulation of cell proliferation, differentiation and survival. Downregulation of the MEK cascades has been implicated in acquiring of the malignant phenotype in various cancers. Somatic mutations in MEK1 gene (substitutions K57N, Q56P, D67N) were described in < 1 % of non-small cell lung cancer (NSCLC) and they were more commonly reported in adenocarcinoma patients with current or former smoking status. Materials and methods: In the following study, we assessed the MEK1 gene mutations in 145 FFPE tissue samples from central nervous system (CNS) metastases of NSCLC using HRM-PCR and ASP-qPCR techniques. The studied group was heterogeneous in terms of histopathology and smoking status. The prevalence of the MEK1 gene mutation was correlated with the occurrence of mutations in KRAS, EGFR, DDR2, PIK3CA, NRAS, HER2, AKT1 and PTEN genes. Results: Using HRM and ASP-qPCR methods we identified one (0.7 %; 1/145) MEK1 substitution (Q56P) in CNS metastases of NSCLC. The mutation was identified in a single, 50-year-old, current smoking men with adenocarcinoma (1.25 %; 1/80 of all adenocarcinomas). Conclusions: According to the current knowledge, the incidence of MEK1 gene mutation in CNS metastatic lesion of NSCLC is the first such report worldwide. The analysis of gene profile in cancer patients may extend the scope of molecularly targeted therapies used both in patients with primary and metastatic tumors of NSCLC (AU)

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Sensitive methods for screening of the MEK1 gene mutations in patients with central nervous system metastases of non-small cell lung cancer.

BACKGROUND: The mitogen-activated protein kinases 1 and 2 (MEK1, MEK2) are fundamental partners in the RAS-RAF-MEK-ERK pathway that is involved in regulation of cell proliferation, differentiation and survival. Downregulation of the MEK cascades has been implicated in acquiring of the malignant phenotype in various cancers. Somatic mutations in MEK1 gene (substitutions K57N, Q56P, D67N) were described in <1 % of non-small cell lung cancer (NSCLC) and they were more commonly reported in adenocarcinoma patients with current or former smoking status. MATERIALS AND METHODS: In the following study, we assessed the MEK1 gene mutations in 145 FFPE tissue samples from central nervous system (CNS) metastases of NSCLC using HRM-PCR and ASP-qPCR techniques. The studied group was heterogeneous in terms of histopathology and smoking status. The prevalence of the MEK1 gene mutation was correlated with the occurrence of mutations in KRAS, EGFR, DDR2, PIK3CA, NRAS, HER2, AKT1 and PTEN genes. RESULTS: Using HRM and ASP-qPCR methods we identified one (0.7 %; 1/145) MEK1 substitution (Q56P) in CNS metastases of NSCLC. The mutation was identified in a single, 50-year-old, current smoking men with adenocarcinoma (1.25 %; 1/80 of all adenocarcinomas). CONCLUSIONS: According to the current knowledge, the incidence of MEK1 gene mutation in CNS metastatic lesion of NSCLC is the first such report worldwide. The analysis of gene profile in cancer patients may extend the scope of molecularly targeted therapies used both in patients with primary and metastatic tumors of NSCLC.

Allergic alveolitis due to herb dust exposure.

We report an episode of allergic alveolitis in a female farmer due to massive exposure to organic dust contaminated with microorganisms during threshing of herbs (thyme). The patient's medical history, the results of exposure test, inhalation challenge, and bronchoalveolar lavage suggested the diagnosis of allergic alveolitis

[Phenotype of lymphocytes in bronchoalveolar lavage and peripheral blood with different clinical presentations of sarcoidosis]. / Fenotyp limfocytów z plukania oskrzelowo-pecherzykowego i krwi obwodowej w róznych postaciach klinicznych sarkoidozy.

The aim of this study was to investigate the relationship between the bronchoalveolar cell counts, the phenotypic characteristics of bronchoalveolar lavage and peripheral lymphocytes and the clinical manifestation of sarcoidosis. 24 patients with sarcoidosis of the lung were examined. Patients were divided into groups based on the presence and the type of clinical symptoms (patients with symptoms of Löfgren syndrome, with constitutional and respiratory symptoms and symptomless patients). The lymphocyte subtypes were analysed using the panel of monoclonal antibodies Simultest IMK Plus with the flow cytometry (Orto Cytoron Absolute). The highest ratio CD4/CD8 in BALF was found in patients with symptoms of Löfgren Syndrome (mean 11.4), the lowest in symptomless patients (mean 4.5). The bronchoalveolar cell count and the percentages of phenotypes of peripheral blood lymphocytes did not differ significantly between the groups of patients. The bronchoalveolar lavage performed in patients with sarcoidosis indicates various intensity of alveolitis dependent on the clinical manifestation.

[Effect of beta 2-adrenergic agonists on neurotoxic action of aminophyllines]. / Wplyw agonistów beta 2-adrenergicznych na neurotoksyczne dzialanie aminofiliny.

The purpose of the present investigation was to evaluate whether the beta 2-adrenergic agonists affect the pharmacodynamics and pharmacokinetics of aminophylline-induced seizures. Adult male Albino Swiss mice were treated i.p. with salbutamol, fenoterol or terbutaline and 30 min. later they received i.p.aminophylline. During 90 min. observation clonic and tonic seizures and also mortality of mice were registered. Moreover the influence of beta 2-adrenomimetics on electroshock-induced seizure threshold (CS 50) and on plasma aminophylline concentration was estimated. It was found that pretreatment with salbutamol, fenoterol and terbutaline decreased the ED 50 (for clonic and tonic seizures) and LD 50 of aminophylline. Fenoterol decreased but terbutaline increased the CS 50 in mice. Only terbutaline elevated significantly the plasma concentration of aminophylline. The data indicate that concomitant treatment with beta 2-adrenergic agonists together with aminophylline increase the risk of aminophylline-induced seizures. Thus plasma monitoring of aminophylline concentration could be used in all patients treated simultaneously with beta-2-adrenergic agonists and aminophylline.

[Clinical evaluation of efficacy and tolerance of oral treatment with ambroxol in patients with chronic bronchitis]. / Ocena kliniczna skutecznosci i tolerancji doustnego leczenia ambrosolem u chorych na przewlekle zapalenie oskrzeli.

This study was designed to examine the efficacy and tolerability of ambroxol (Ambrosol) on the symptomatology of chronic bronchitis among in- and out-patients. Seventy patients were included in the trial and divided into two random groups. The patients were treated in a double-blind way with either Ambrosol or a placebo for 2 months. The physician and the patient assessed the following points: the feeling general well-being, the symptoms of a cold and of fever, the need for treatment with antibiotics, the amount, viscosity and colour of sputurn, the difficulty in expectoration, the severity of coughing and any changes in breathlessness while at rest. In order to carry out these subjective assessments we used a scoring system. We observed that, breathlessness while at rest and the rate of exacerbation was significantly lower in the Ambrosol group after 2 weeks of therapy. Sputum viscosity, difficulty in expectoration and severity of coughing were reduced in this group after 4 or 8 weeks. Throughout the 2-month period of therapy, the tolerability of ambroxol was good. A total of 4 patients reported side-effects of various degrees of severity. One patient stopped the therapy due to these side-effects (dizziness). There was no significant difference in the number of side-effects between the two groups (Ambrosol vs Placebo).

[The effect of fiberoptic bronchoscopy and bronchoalveolar lavage (BAL) on results of spirometric measurements]. / Wplyw bronchofiberoskopii i plukania oskrzelowo-pecherzykowego (BAL) na wyniki badania spirometrycznego.

The effect of fiberoptic bronchoscopy and bronchoalveolar lavage on the functioning of the respiratory system was studied in 72 patients (42 males and 30 females). The bronchoscopy was performed in the sitting position. Supplemental oxygen was not given to all the evaluated patients. The group included 24 patients with lung cancer, 9 with sarcoidosis, 12 with tuberculosis, 1 with farmer's lung and 10 with other lung diseases (pneumonia, COPD). A control group consisted of 16 patients who were undergoing routine diagnostic endoscopy but who were seen to be without lung disease. Group BF (39 individuals) received only a bronchoscopic examination, group BF+BAL (33 persons) received a bronchoscopy followed by BAL using 140 ml. of normal saline solution as a lavage fluid. After the bronchoscopic examination there were significant differences in all spirometric measurements, except MEF25. The bronchoscopy and bronchoalveolar lavage caused a transient fall in FEV1, VC, MEF50, MEF75 (7.7-9.4%) which was similar in both groups. These measurements returned to normal after 24 hours. The testing of pulmonary functioning before the bronchoscopy was seen to be clinically important for safety of the patient undergoing this procedure.