Towards optimizing the protocol for untargeted profiling of urine volatiles via gas chromatography-ion mobility spectrometry. A pilot study.

The analysis of volatile organic compounds (VOCs) present in various biological samples holds immense potential for non-invasive disease diagnostics and metabolic profiling. One of the biological fluids that are suitable for use in clinical practice is urine. Given the limited quantity of VOCs in the urine headspace, it's imperative to enhance their extraction into the gaseous phase and prevent any degradation of VOCs during the thawing process. The study aimed to test several key parameters (incubation time, temperature, and thawing) that can influence urine volatilome and monitor selected VOCs for their stability. The analysis in this study was performed using a BreathSpec® (G.A.S., Dortmund, Germany) device consisting of a gas chromatograph (GC) coupled with an ion mobility spectrometer (IMS). Testing three different temperatures and incubation times yielded a low number of VOCs (9 out of 34) that exhibited statistically significant differences. However, examining three thawing conditions revealed no VOCs with statistically significant changes. Thus, we conclude that urine composition remains relatively stable despite exposure to various thermal stresses.

Lung ultrasound could reduce X-ray after major lung resection.

OBJECTIVES: This study evaluated the role of ultrasound in postoperative care after major lung resection. BACKGROUND: High accuracy of lung ultrasound imaging was proved in various medical fields. The experience with ultrasound after thoracic surgery is limited. METHODS: Patients scheduled for major lung resection were consecutively included in a prospective study comparing two modalities of imaging examinations, namely those employing ultrasound and X-ray in the diagnoses of pneumothorax and pleural effusion. Two examinations were performed. One after recovery from anaesthesia, the second before chest tube removal. RESULTS: Forty-eight patients underwent 87 examinations. X-ray and ultrasound examinations showed substantial and fair agreements for pneumothorax (Cohen's kappa coefficients 0.775 and 0.397) and slight and substantial agreements for pleural effusion (Cohen's kappa coefficients 0.036 and 0.611). The sensitivity bounds for pneumothorax were 45.5-58.5 % at the first and 29.7-59.4 % at the second examination. Sensitivity bounds for pleural effusion were 0-86.2 % at the first and 32.6-36.9 % at the second examination. Except for two cases of pneumothorax being missed by X-ray imaging, the rest of mismatches were clinically irrelevant conditions with no impact on clinical decision and patient's outcome. CONCLUSION: The use of ultrasound can reduce the number of X-ray examinations and thus lower the radiation exposure after major lung resections (Tab. 4, Ref. 30).

The Role of Dysregulated MicroRNA Expression in Lung Cancer.

MicroRNAs (miRNAs) are a class of small single-stranded non-protein-coding RNAs that play important regulatory roles in many cellular processes including cell proliferation, differentiation, growth control, and apoptosis. They regulate gene expression on the posttranscriptional level by translational repression, mRNA cleavage, or mRNA degradation in various physiological and pathological processes. In addition, some miRNAs can function as oncogenes or tumor suppressors, so they can regulate several genes that play important roles in tumorigenesis. It was found that miRNAs are directly involved in many types of cancer, including lung cancer. Lung cancer is the leading cause of cancer mortality worldwide with a substantially low survival rate. In this work, we summarize recent findings related to miRNAs mechanisms of action and the role of their dysregulated expression in lung tumorigenesis. We describe the most important miRNAs involved in lung cancer development and targets of their activity. The understanding of the miRNA regulation in cancer may help better understand the molecular mechanisms of tumorigenesis and their importance in cancerous transformation.

Associations of CYP1A2 Polymorphisms with the Risk Haplotypes in Lung Cancer in the Slovak Population.

Phase I enzymes, including cytochrome P450, family 1, subfamily A, and polypeptide 2 (CYP1A2), are involved in the activation of carcinogens to reactive intermediates that are capable of binding covalently to DNA to form DNA adducts, potentially initiating the carcinogenic process. The aim of present study was to investigate the association of CYP1A2 gene polymorphisms and haplotypes with lung cancer risk. A case-control study was carried out on 105 lung cancer patients and 189 controls. To investigate three CYP1A2 polymorphisms: rs2472299, rs2470890, rs11072508 we used a high resolution melting analysis. We found significant allele associations (rs2470890 and rs2422299) with lung cancer risk. We searched for meaningful associations for all variants in the dominant, recessive, and additive genetic models. Genotype associations in the recessive model were of marginal significance for the same single nucleotide polymorphisms. A haplotype analysis included five variants with the frequency higher than 1 %. The haplotype "acc", present with the highest frequency, was associated with increased lung cancer risk (38.7 % vs. 31.5 %; OR 1.38; 95 %CI 0.95-2.01). On the contrary, rare haplotype "gtc" was significantly associated with decreased lung cancer risk in the Slovak population. In conclusion, the present study identified the risk alleles and haploid genotype associations of the CYP1A2 gene in lung cancer.

Polymorphisms of Selected DNA Repair Genes and Lung Cancer in Chromium Exposure.

Chromium is a well-known mutagen and carcinogen involved in lung cancer development. DNA repair genes play an important role in the elimination of genetic changes caused by chromium exposure. In the present study, we investigated the polymorphisms of the following DNA repair genes: XRCC3, participating in the homologous recombination repair, and hMLH1 and hMSH2, functioning in the mismatch repair. We focused on the risk the polymorphisms present in the development of lung cancer regarding the exposure to chromium. We analyzed 106 individuals; 45 patients exposed to chromium with diagnosed lung cancer and 61 healthy controls. Genotypes were determined by a PCR-RFLP method. We unravelled a potential for increased risk of lung cancer development in the hMLH1 (rs1800734) AA genotype in the recessive model. In conclusion, gene polymorphisms in the DNA repair genes underscores the risk of lung cancer development in chromium exposed individuals.

[Surgical Treatment of Lung Metastases of Colorectal Carcinoma -  Survival and Prognostic Factors]. / Chirurgická liecba plúcnych metastáz kolorektálneho karcinómu -  prezívanie a prognostické faktory.

BACKROUND: Colorectal carcinoma has the third highest incidence of all tumor diseases in the world. In the long term, Slovak republic is among countries with highest occurrence of this disease. About 25% of patients have distant metastases at the time of diagnosis, and about 50% of patients progress. The first possibility of colorectal carcinoma lung metastases treatment is metastasectomy which may have a curative character. MATERIALS AND METHODS: In this paper, the authors retrospectively evaluated 50 patients who had undergone surgical treatment to establish the diagnosis of colorectal carcinoma lung metastases at the Clinic of thoracic surgery of JLF UK and UH Martin between 2003 and 2014. RESULTS: Altogether, 27 men and 23 women were operated (average age: 62 and 61 years). 52% of patients had solitary metastasis.We chose thoracotomy as a surgical access for majority of the surgeries (76%), and the most common type of surgical procedure was a wedge resection (74%). 3-year survival of patients after complete metastasectomy was 55.5%, and 5-year survival was 31.8% with a median survival of 42 months. We did not record any statistically significant influence of number of metastases (p = 0.3297) and length of disease-free interval (p = 0.4423) on the long-term survival, but we confirmed a significant difference of survival in different prognostic groups according to the International registry of lung metastases (p = 0.049). CONCLUSION: A surgical removal of colorectal carcinoma lung metastases in selected patients is an important curative modality that might prolongsurvival, improve the prognosis and at the same time have minimum complications. The results show that the strongest predicative indicator of prognosis is incorporation of the patients to the prognostic groups determined by the International Registry of Lung Metastases.

Lung adenocarcinoma and squamous cell carcinoma in association with genetic polymorphisms of GSTs in Slovak population.

Slovak Republic belongs to the countries with high incidence of lung cancer. Gene polymorphisms of the glutathione S-transferases (GSTs) may play a role in individual lung cancer susceptibility. In presented case-control study we investigate the incidence of polymorphism of GSTT1, GSTM1, GSTP1 genes and their combinations as possible predictive factors for identification of individuals with increased risk of formation and development of adenocarcinoma (AC) and squamous cell carcinoma (SCC) of lung in Slovak population. The study was conducted on 520 individuals consisting of 118 patients with adenocarcinoma, 112 patients with squamous cell carcinoma and 290 control individuals. GSTT1, GSTM1, GSTP1 gene polymorphisms were assayed by standard PCR and PCR-RFLP technique. The results of this study indicate that the GSTT1null-genotype and combination GSTT1 null and Ile/Val or Val/Val are associated with increased risk of lung adenocarcinoma. A significant association with 2.13 - fold increased risk was observed between lung adenocarcinoma and GSTT1 null genotype (95% CI = 1.29 - 3.51; p= 0.004). Also it was proved 2.83 times statistically higher risk for development of this histological type of lung cancer (95% CI = 1.34 - 6.01; P= 0.005) in combination of GSTT1null and Ile/Val or Val/Val genotypes. GSTT1, GSTM1, GSTP1 polymorphism did not show any significant association with SCC. Our study suggests that genetic make-up in metabolizing genes may increase susceptibility towards lung cancer development.

[Lung pneumatocele in adult patient - case report]. / Plúcna pneumatokéla u dospelého pacienta - kazuistika.

Lung pneumatoceles are characterized by a thin-walled air-filled cavity present in lung parenchyma. Mostly they are the result of acute bronchopneumonia after spontaneous drainage of altered lung parenchyma with subsequent development and progression of cavities due to ventile mechanism. This disease is more prevalent in infants and young children, it is rather rare in adults. In the present case report, videothoracoscopy resection of lung pneumatocele of the right lower lobe was performed a 43-years old man. The operation was indicated for the presence of chronic persisting and progressing pneumatocele as a preventive measure of pneumatocele complications.

[Five year-results of chemoresistance testing in cancer patients]. / Nase pät'rocné výsledky in vitro testovania chemorezistencie u onkologických pacientov.

BACKGROUNDS: Translational medicine is a medical field encompassing basic research and development of new diagnostic and therapeutic strategies for clinical practice. The present scientific paper focuses on our previous experience in the field of chemoresistance testing in patients with oncological diseases. MATERIAL AND METHODS: Since 2005, we sampled 71 patients with a leukaemia (AML, ALL and CML) and 92 patients with a solid tumour (lung and gastrointestinal tract cancer). Malignant cell in vitro drug resistance testing was carried out using cytotoxic methyl-thiazol tetrazolium (MTT) assay. RESULTS: Based on the LC50 (lethal concentration of a drug killing 50% of cell population), we found that patients with acute myeloblastic leukaemia exhibit a greater degree of resistance than patients with acute lymphoblastic leukaemia. In patients with bronchogenic carcinomas, primary resistance to cisplatin was identified in 28% of tested samples, paclitaxel 36%, vincristine 50%, etoposide 56%, vinorelbine 57%, topotecan 62%, gemcitabine 77% and dacarbazine 86%. CONCLUSION: In vitro tests with gastrointestinal tract cancers also suggested high effectiveness of cisplatin (with the exception of gastric carcinoma) that was comparable with 5-fluorouracil. Even though the MTT assay has some limitations (insufficient number of vital cells, possible contamination by non-malignant cells, etc.), this in vitro method proved very effective in testing malignant cell resistance to clinically used cytostatics.

[Lung hernia following limited thoracotomy]. / Hernia pl'uc po limitovanej torakotómií.

Authors in the adduced work in the form of case report introduce a case of lung herniation as a rare complication after limited thoracotomy. Also on the strength of published literature they briefly discuss about the causes of genesis of lung hernia and the possibilities of their operative solution.

Polymorphisms of biotransforming enzymes (GSTs) and their association with colorectal cancer in the Slovak population.

The aim of present study was to summarize the results of a case-control study focused on genetic polymorphisms of selected Phase II metabolizing enzymes (GSTM1, T1, P1) and to investigate the association of these polymorphisms with the colorectal cancer risk among the Slovak population. A case-control study with 183 colorectal cancer cases and 422 controls was conducted. DNA was extracted from peripheral blood leukocytes, and the polymorphisms of GSTM1, GSTT1 and GSTP1 enzymes were determined by PCR-based methods. Association between specific genotypes and the development of colorectal cancer were examined using logistic regression analysis to calculate odds ratios (OR) and 95% confidence intervals (CI). The GSTP1 val/val genotype (OR=2.1, 95%CI: 1.1 - 4.0, chi2 = 0.28 and P = 0.0025) was associated with an elevated risk. The statistically significant correlation was found also for the combined genotypes of GSTM1 null and GSTP1 valine homozygosity (OR = 2.7, 95% CI: 1.1-6.1, chi2 = 4.5 and P = 0.03). The genotype of certain metabolising enzymes affects the risk for colorectal cancer. This effect is also important when certain allelic combinations are studied. In the near future, individual risk assessment may be reached by further increasing the number of studies of polymorphisms, combining them with the traditional epidemiological risk factor.

Gene polymorphisms of biotransforming enzymes (GSTs) and their association with lung cancer in the Slovakian population.

OBJECTIVE: The aim of present study was to present the results of a case-control study focused on genetic polymorphisms of selected Phase II metabolizing enzymes (GSTM1, T1, and P1) and to investigate the association of these polymorphisms with lung cancer risk in the Slovakian population. MATERIAL AND METHODS: The study encompassed 160 lung cancer cases and 220 controls. DNA was extracted from peripheral blood leukocytes, and the polymorphisms of GSTM1, GSTT1 and GSTP1 enzymes were determined by PCR-based methods. We determined the genotype distribution of all these genes and their combinations. The association between specific genotypes and the development of lung cancer were examined using logistic regression analysis to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: We found that the GSTM1 null genotype (OR=1.6; 95% CI=1.03-2.4; chi(2)=4.08, and P=0.04) was associated with elevated risk. A significant correlation also was found for the combined genotypes of GSTM1 null and GSTP1 Ile/Val and Val/Val (OR=2.01; 95% CI=1.1-6.1; chi(2)=3.6, and P=0.02) and GSTM1 null and GSTT1 positive (OR=2.00; 95% CI=1.2-3.2; chi(2)=7.3, and P=0.006). CONCLUSIONS: We conclude that the genotype of metabolizing enzymes and allelic combinations underscore the risk for lung cancer. Individual risk assessment may be further improved by increasing the number of polymorphisms studied and combining them with the traditional epidemiological risk factor.