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Öğe Diagnosis of malignant pleural mesothelioma from pleural fluid by Fourier transform-infrared spectroscopy coupled with chemometrics(Spie-Soc Photo-Optical Instrumentation Engineers, 2018) Abbas, Sherif; Özek, Nihal Şimşek; Emri, Salih; Köksal, Deniz; Severcan, Mete; Severcan, FerideThis study was conducted to differentiate malignant pleural mesothelioma (MPM) from lung cancer (LC) and benign pleural effusion (BPE) from pleural fluids using the diagnostic power of Fourier transform-infrared spectroscopy with attenuated total reflectance mode coupled with chemometrics. Infrared spectra of MPM (n = 24), LC (n = 20), and BPE (n = 25) were collected, and hierarchical cluster analysis (HCA) and principal component analysis (PCA) were applied to their spectra. HCA results indicated that MPM was differentiated from LC with 100% sensitivity and 100% specificity and from BPE, with 100% sensitivity and 88% specificity, which were also confirmed by PCA score plots. PCA loading plots indicated that these separations originated mainly from lipids, proteins, and nucleic acids-related spectral bands. There was significantly higher lipid, protein, nucleic acid, and glucose contents in the MPM and LC. However, the significant changes in triglyceride and cholesterol ester content, protein and nucleic acid structure, a lower membrane fluidity, and higher membrane order were only observed in the MPM. To check the classification success of some test samples/each group, soft independent modeling of class analogies was performed and 96.2% overall classification success was obtained. This approach can provide a rapid and inexpensive methodology for the efficient differentiation of MPM from other pleural effusions. (C) 2018 Society of Photo-Optical Instrumentation Engineers (SPIE)Öğe Diagnosis of malignant pleural mesothelioma from pleural fluid by Fourier transform-infrared spectroscopy coupled with chemometrics (vol 23, 105003, 2018)(Spie-Soc Photo-Optical Instrumentation Engineers, 2018) Abbas, Sherif; Ozek, Nihal Simsek; Emri, Salih; Koksal, Deniz; Severcan, Mete; Severcana, FerideChlorobenzene is a commonly used toxic solvent and listed as a priority environmental pollutant by the US Environmental Protection Agency. Here, we report that Escherichia coli TG1 cells expressing toluene o-xylene monooxygenase (ToMO) can successfully oxidize chlorobenzene to form dihydroxy chloroaromatics, which are valuable industrial compounds. Toluene o-xylene monooxygenase (ToMO) was found to oxidize chlorobenzene to form 2-chlorophenol (2-CP, 4%), 3-CP (12%), and 4-CP (84%) with a total product formation rate of 1.2 +/- 0.17 nmol/min/mg protein. It was also discovered that ToMO forms 4-chlorocatechol (4-CC) from 3-CP and 4-CP with initial rates of 0.54 +/- 0.10 and 0.40 +/- 0.04 nmol/min/mg protein, respectively, and chlorohydroquinone (CHQ, 13%), 4-chlororesorcinol (4-CR, 3%), and 3-CC (84%) from 2-CP with an initial product formation rate of 1.1 +/- 0.32 nmol/min/mg protein. To increase the oxidation rate and alter the oxidation regiospecificity of chloroaromatics, as well as to study the roles of active site residues L192 and A107 of the alpha hydroxylase fragment of ToMO (TouA), we used the saturation mutagenesis approach of protein engineering. Thirteen TouA variants were isolated, among which some of the best substitutions uncovered here have never been studied before. Specifically, TouA variant L192V was identified which had 1.8-, 1.4-, 2.4-, and 4.8-fold faster hydroxylation activity toward chlorobenzene, 2-CP, 3-CP, and 4-CP, respectively, compared to the native ToMO. The L192V variant also had the regiospecificity of chlorobenzene changed from 4% to 13% 2-CP and produced the novel product 3-CC (4%) from 3-CP. Most of the isolated variants were identified to change the regiospecificity of oxidation. For example, compared to the native ToMO, variants A107T, A107N, and A107M produced 6.3-, 7.0-, and 7.3-fold more 4-CR from 2-CP, respectively, and variants A107G and A107G/L192V produced 3-CC (33 and 39%, respectively) from 3-CP whereas native ToMO did not. IMPORTANCE Chlorobenzene is a commonly used toxic solvent and listed as a priority environmental pollutant by the US Environmental Protection Agency. Here, we report that Escherichia coli TG1 cells expressing toluene o-xylene monooxygenase (ToMO) can successfully oxidize chlorobenzene to form dihydroxy chloroaromatics, which are valuable industrial compounds. ToMO performs this at room temperature in water using only molecular oxygen and a cofactor supplied by the cells. Using protein engineering techniques, we also isolated ToMO variants with enhanced oxidation activity as well as fine-tuned regiospecificities which make direct microbial oxygenations even more attractive. The significance of this work lies in the ability to degrade environmental pollutants while at the same time producing valuable chemicals using environmentally benign biological methods rather than expensive, complex chemical processes.Öğe Diagnostic utility of conventional transbronchial needle aspiration in older patients(Springer Heidelberg, 2018) Ulaşlı, Sevinç Sarınç; Köksal, Deniz; Karcıoğlu, Oğuz; Babaoğlu, Elif; Önder, Sevgen; Emri, Salih; Babaoğlu, ElifBackground In older patients, diagnosis and initial treatment should be considered as soon as possible because of high disease burden and complications. Conventional transbronchial needle aspiration (C-TBNA) is an important and safe method for the diagnosis of mediastinal lesions and staging lung cancer in the general population. We aimed to evaluate the diagnostic utility and complications of C-TBNA procedure in older patients aged >= 65 years. Method We retrospectively evaluated C-TBNA results consecutively. Demographic data, clinical, radiological and flexible bronchoscopy (FB) findings, complications during C-TBNA and incidence of diagnostic C-TBNA with the presence of abundant lymphoid cells of polymorphous appearance both in patients aged >= 65 years and in younger patients were determined. Results C-TBNA was performed to a total of 317 patients, including 109 older and 208 younger patients attended to our clinic between 2012 and 2016. The mean ages of older and younger patients were 70.3 +/- 4.6 and 52.5 +/- 10 years, respectively (p < 0.001). Overall, 75.2% of older and 80.3% of younger patients had diagnostic C-TBNA. The diagnostic utility of C-TBNA did not differ significantly between older and younger patients (p = 0.297). During C-TBNA, one older patient had a complication of bronchospasm, and four younger patients had complications such as bleeding (n = 1) and bronchospasm (n = 3). There was no statistically significant difference between older and younger patients in terms of complications during C-TBNA procedure (p = 0.49). Conclusion C-TBNA is a safe procedure with similar diagnostic yield in older patients.Öğe Infrared spectroscopy offers tremendous potential in cancer diagnosis(Cell Press, 2019) Severcan, Feride; Abbas, Sherif; Yonar, Dilek; Emri, SalihAll over the word, scientists are actively engaged in the characterization, screening and diagnosis of different pathological conditions. Ideally, the aim is to monitor the system of interest, without disturbing it, in a sensitive, rapid and operated manner at minimum cost.Öğe Rapid diagnosis of malignant pleural mesothelioma and its discrimination from lung cancer and benign exudative effusions using blood serum(2022) Yonar, Dilek; Severcan, Mete; Gurbanov, Rafig; Sandal, Abdulsamet; Yılmaz, Ülkü; Emri, Salih; Severcan, FerideMalignant pleural mesothelioma (MPM), an aggressive cancer associated with exposure to fibrous minerals, can only be diagnosed in the advanced stage because its early symptoms are also connected with other respiratory diseases. Hence, understanding the molecular mechanism and the discrimination of MPM from other lung diseases at an early stage is important to apply effective treatment strategies and for the increase in survival rate. This study aims to develop a new approach for characterization and diagnosis of MPM among lung diseases from serum by Fourier transform infrared spectroscopy (FTIR) coupled with multivariate analysis. The detailed spectral characterization studies indicated the changes in lipid biosynthesis and nucleic acids levels in the malignant serum samples. Furthermore, the results showed that healthy, benign exudative effusion, lung cancer, and MPM groups were successfully separated from each other by applying principal component analysis (PCA), support vector machine (SVM), and especially linear discriminant analysis (LDA) to infrared spectra.Öğe The role of peak oxygen consumption measurement in predicting postoperative pulmonary complications in patients with early stage lung cancer(European Respiratory Soc Journals Ltd, 2018) Ibrahimov, Ferhad; Köksal, Deniz; Ulaşlı, Sevinç Sarınç; Dikmen, Erkan; Yılmaz, Yiğit; Babaoğlu, Elif; Emri, SalihIntroduction: The best survival rates are achieved in early stage lung cancer patients who had undergone surgical resection. Cardiopulmonary Exercise Testing (CPET) is an important preoperative test because of its ability to detect disturbance in oxygen transport system which inturn is related to development of postoperative complications. The aim of this study is to identify the value of peak oxygen consumption (peakVO2) measurement in predicting postoperative pulmonary complications (PPCs). Methods: Lung cancer patients who are candidates for surgery between Feb 2015- Feb 2017 were included in this propectively conducted study. PeakVO2 measurement was performed by utilizing cycle ergometry with the current system ""Fitmate®Med"" during incremental exercise. All patients were on follow-up for PPCs for a period of 30 days postoperatively. Results: The study included 41 patients (mean age:63.9±9.7 years) who had undergone surgical resection (28 lobectomy/13 pneumonectomy) in our hospital. There was no mortality; but 8 (19.5%) PPCs. Mean peakVO2 value wasn't different in patients with and without PPCs. When the patients were divided into two groups based on absolute FEV1 (≤1.5 L and >1.5 L) and ppoFEV1% (≤%30 and >%30), mean peakVO2, mean staying days in intensive care and hospital, PPC rates were similar between groups. 14 patients who had a FEV1 ≤1.5 L; 11 patients who had a ppoFEV1 ≤%30 underwent successful surgical resections. Conclusion: PeakVO2 measurement prevents patients to be deprived of a surgical resection that is an important treatment modality for lung cancer. PPCs were in acceptable limits in patients with adequate peakVO2 values.Öğe Triple test with tumor markers CYFRA 21.1, HE4, and ProGRP might contribute to diagnosis and subtyping of lung cancer(Pergamon-Elsevier Science Ltd, 2018) Korkmaz, Elif Tuğçe; Köksal, Deniz; Aksu, Funda; Dikmen, Z. Günnür; İçen, Duygu; Maden, Emin; Emri, SalihBackground and aim: Early diagnosis and histological subtyping are important issues in the management of patients with lung cancer (LC). The aim of this study is to investigate the diagnostic value of a panel of serum tumor markers in newly diagnosed patients with LC. Methods: Venous blood samples were collected from 99 patients with LC (42 adenocarcinoma, 35 squamous, and 22 small cell carcinoma) and 30 patients with benign lung disease. Progastrin releasing peptide (ProGRP), squamous cell carcinoma antigen (SCCAg), cytokeratin 19-fragments (CYFRA 21.1), human epididymis protein 4 (HE4), Chromogranin A (CgA) and neuron specific enolase (NSE) levels were measured. The diagnostic value of the biomarkers was assessed with ROC curve analyses; the area under the curve (AUC) was calculated. Results: Serum CYFRA 21.1, ProGRP, SCCAg, NSE levels were significantly higher in LC patients. While ProGRP levels were higher (p = 0.009) in SCLC; CYFRA 21.1 and SCCAg levels were higher in NSCLC (p = 0.019 and p = 0.001, respectively). The sensitivity and specificity of tumor markers were 72%, 83% for CYFRA 21.1; 70%, 57% for HE4; 18%, 93% for ProGRP; 43%, 77% for SCCAg; 54%, 53% for CgA; 73%, 50% for NSE. CYFRA 21.1 (p < 0.001, r = 0.394), HE4 (p = 0.014, r = 0.279) and CgA (p = 0.023, r = 0.259) levels were positively correlated with tumor stage in NSCLC. CgA levels were significantly higher in extensive stage SCLC (p = 0.004). CYFRA 21.1 had the highest diagnostic value for LC (AUC = 0.865). When it is combined with HE4, diagnostic value increased (AUC = 0.899). ProGRP had the highest diagnostic value (AUC = 0.875, p < 0.001) for discriminating SCLC from NSCLC. Conclusion: A panel of three tumor markers CYFRA 21.1, HE4 and ProGRP may play a role for discriminating LC from benign lung disease and subtyping as SCLC.
