Sputum Microbiome Composition in Patients with Squamous Cell Lung Carcinoma.

BACKGROUND: Recent findings indicate that the host microbiome can have a significant impact on the development of lung cancer by inducing an inflammatory response, causing dysbiosis, and generating genome damage. The aim of this study was to search for bacterial communities specifically associated with squamous cell carcinoma (LUSC). METHODS: In this study, the taxonomic composition of the sputum microbiome of 40 men with untreated LUSC was compared with that of 40 healthy controls. Next-Generation sequencing of bacterial 16S rRNA genes was used to determine the taxonomic composition of the respiratory microbiome. RESULTS: There were no differences in alpha diversity between the LUSC and control groups. Meanwhile, differences in the structure of bacterial communities (ß diversity) among patients and controls differed significantly in sputum samples (pseudo-F = 1.53; p = 0.005). Genera of Streptococcus, Bacillus, Gemella, and Haemophilus were found to be significantly enriched in patients with LUSC compared to the control subjects, while 19 bacterial genera were significantly reduced, indicating a decrease in beta diversity in the microbiome of patients with LUSC. CONCLUSIONS: Among other candidates, Streptococcus (Streptococcus agalactiae) emerges as the most likely LUSC biomarker, but more research is needed to confirm this assumption.

Rogue versus chromothriptic cell as biomarker of cancer.

New molecular cytogenetic biomarkers may significantly contribute to biodosimetry, whose application is still globally diverse and not fully standardized. In 2011, a new term, chromothripsis, was introduced raising great interest among researchers and soon motivating further investigations of the phenomenon. Chromothripsis is described as a single event in which one or more chromosomes go through severe DNA damage very much resembling rogue cells (RC) described more than 50 years ago. In this review, we for the first time compare these two multi-aberrant cells types, RC versus chromothriptic cells, giving insight into the similarities of the mechanisms involved in their etiology. In order to make a better comparison, data on RC in 3366 subjects from studies on cancer patients, Chernobyl liquidators, child victims of the Chernobyl nuclear plant accident, residentially and occupationally exposed population have been summarized for the first time. Results of experimental and epidemiological analysis show that chromothriptic cells and RC may be caused by exposure to high LET ionizing radiation. Experience and knowledge collected on RC may be used in future for further investigations of chromothripsis, introducing a new class of cells which include both chromothriptic and RC, and better insight into the frequency of chromothriptic cell per subject, which is currently absent. Both cell types are relevant in investigations of cancer etiology, biomonitoring of accidentally exposed population to ionizing radiation and biomonitoring of astronauts due to their exposure to high LET ionizing radiation during interplanetary voyages.

Polymorphisms in DNA repair genes in lung cancer patients living in a coal-mining region.

Air pollutants and ionizing radiation are well-known carcinogens involved in the pathogenesis of lung cancer, and residents of coal-mining regions are exposed routinely to these agents. Polymorphisms in DNA repair genes may be associated with an increased risk of malignant transformation. We investigated associations between the risk of lung cancer in residents of the coal-mining region and polymorphisms in the genes APEX1 (rs1130409), hOGG1 (rs1052133), XRCC1 (rs25489, rs25487), XRCC2 (rs3218536), XRCC3 (rs861539), ADPRT/PARP1 (rs1136410), XPD/ERCC2 (rs13181), XPG/ERCC5 (rs17655), XPC (rs2228001), ATM (rs1801516), and NBS1 (rs1805794). Three hundred and forty residents of the Kemerovo Region (a coal-mining region of western Siberia) were lung cancer patients exposed to air pollutants and ionizing radiation (case) and 335 were healthy donors (control). Genotyping was performed by real-time PCR and allele-specific PCR. We discovered that polymorphisms in the XPD gene in men [log-additive model: odds ratio (OR) = 1.64, 95% confidence interval (CI): 1.17-2.31], the ATM gene in women and nonsmokers (codominant model: OR = 0.11, 95% CI: 0.02-0.49 and OR = 0.25, 95% CI: 0.08-0.72, respectively), the APEX1 gene for smokers (recessive model: OR = 2.55, 95% CI: 1.34-4.85), and the NBS1 gene for those who work in the coal industry (overdominant model: OR = 0.40, 95% CI: 0.21-0.75) are associated with an increased risk of lung cancer. Using the multifactor dimensionality reduction method, we found a model of gene-gene interactions associated with the risk of lung cancer: NBS1 (rs1805794)-XRCC1 (rs25487)-hOGG1 (rs1052133)-XPG (rs17655). These results indicate an association between combinations of polymorphisms in the studied genes and the risk of lung cancer in residents of a coal-mining region.

Idiotypic and anti-idiotypic antibodies against polycyclic aromatic hydrocarbon in human blood serum are new biomarkers of lung cancer.

Evaluation of epidemiologic risk factor in relation to lung cancer invoked by polycyclic aromatic hydrocarbons has been inconsistent. To address this issue, we conducted a prospective evaluation of new biomarkers for lung cancer classified according levels of idiotypic and anti-idiotypic antibodies against polycyclic aromatic hydrocarbons in human blood serum. The blood serums of 557 lung cancer patients and 227 healthy donors were analysis of these antibodies by ELISA. Collected data were regrouped and analyzed by gender, smoking, and age as predictors of risk lung cancer factors. Also, the data of lung cancer patients were additionally analyzed by stages and types of lung cancer, surgery, and chemotherapy. It was suggested to use ratio of idiotypic and anti-idiotypic antibodies rather than distinguish level each of them separately. The ratio of levels in healthy people was 3.32 times higher than in lung cancer patients. This approach gave more precisely results and great prognostic value. The logistic regression model (AUC = 0.9) and neural networks (AUC = 0.95) were built to compare lung cancer patients and healthy donors by predictors. The ELISA data of 49 people random sampled from the originally ELISA data and ELISA data of 52 coal miners as a group of lung cancer risk were confirmed logistic regression model. So, suggested idiotypic and anti-idiotypic antibodies against polycyclic aromatic hydrocarbons were not only shown difference between healthy donors and lung cancer patients also elicited group of lung cancer risk among healthy people.

Chromosome aberrations in peripheral blood lymphocytes of lung cancer patients exposed to radon and air pollution.

Lung cancer is one of the most common forms of cancer. The aim of this study was to validate chromosome aberrations in peripheral blood lymphocytes of lung cancer patients living in a region with high air pollution and increased background radon levels as a biomarker of cancer risk. A total of 417 lung cancer patients and 468 control participants were analysed using a chromosome aberration assay in peripheral blood lymphocytes. The results showed that chromatid-type aberrations (2.26±1.58 vs. 1.60±1.58) and chromosome-type aberrations (CSAs) (0.96±1.36 vs. 0.42±0.70) in lung cancer patients were increased significantly in comparison with the controls. The most significant two-fold increase was detected for CSAs (nonsmoking patients: 0.84±1.54 vs. 0.41±0.73%, smoking patients: 0.99±1.31 vs. 0.44±0.67%). The frequency of dicentric and ring chromosomes, double minutes and rogue cells was significantly higher (P=0.002, 0.00002, 0.01, 0.0007) in the lung cancer patients. As both analysed groups lived in the same environment, our results show that increased radon levels were not the only source for the detected genome damage. Using binomial logistic regression, the estimated odds ratios and 95% confidence intervals adjusted for the main confounders (smoking, occupational exposure, age) were 1.31 (1.20-1.40) for chromatid-type aberrations, 1.28 (1.17-1.33), and 1.68 (1.49-1.88) for CSAs. It may be suggested that lung cancer patients show a significant increase in genome damage that may be caused by an interplay between exposure and individual low capacity of DNA repair, leading to genome instability.

Dielectric and Mössbauer studies of ferroelectric and magnetic phase transitions in A-site and B-site substituted multiferroic PbFe0.5Nb0.5O3.

In the present study, we diluted either A- or B- sublattice of perovskite multiferroic PbFe(0.5)Nb(0.5)O(3) (PFN) and studied the changes of the magnetic and ferroelectric phase transition temperatures and dielectric properties caused by such dilution. Dielectric studies of PFN single crystals show that, in contrast to the commonly adopted view, the ferroelectric phase transition in PFN is non-diffused and the relaxor-like behavior usually observed in ceramic samples has an extrinsic nature. A-site substitutions (Ba, Ca) lead to the smearing of the permittivity-temperature maximum, lowering its maximum temperature, T(m) and inducing relaxor behavior. B-site diluting of PFN by Ti increases T(m) and only slightly affects the permittivity maximum diffuseness. Both A-site and B-site substitutions in PFN lead to lowering of its Neel temperature, T(N). However, above a certain compositional threshold, fast lowering of T(N) stops and a new magnetic state with comparatively high (~50K) transition temperature becomes stable in a rather wide compositional range.

Dielectric and piezoelectric properties of PbFe1/2Nb1/2O3-PbTiO3 ceramics from the morphotropic phase boundary compositional range.

Dielectric, X-ray, and piezoelectric studies of highly-resistive Li-doped (1-x)PbFe(1/2)Nb(1/2)O(3)-(x)PbTiO(3) (PFN-xPT) ceramics from the 0 ≤ x ≤ 0.2 range fabricated by solid-state synthesis and usual sintering have been carried out. Distinct anomalies of dielectric and piezoelectric parameters, corresponding to the transition between rhombohedral (monoclinic) and tetragonal ferroelectric phases, have been observed in pure PFN and PFN-xPT compositions with PbTiO(3) content up to 8 mol.%. The x,T-phase diagram of the PFN-xPT solid solution system has been constructed using these data.

Transcriptome profiling reveals similarities and differences in plant responses to cadmium and lead.

We analyzed the influence of salts of two heavy metals--lead and cadmium (Pb2+ and Cd2+) on plants, including plant and root size, plant genome stability as well as global genome expression. Measurement of the metal uptake showed that there was a significantly higher incorporation of Cd than of Pb, 0.6 and 0.15 uM per gram of dry weight, respectively. The analysis of the root length and plant size showed a dose dependent decrease in plants exposed to cadmium. In contrast there was little difference in the size of plants exposed to lead, although there was nearly four-fold increase of the root length. Analysis of the genome stability revealed that cadmium led to a dose dependent increase of homologous recombination whereas lead had no effect. Analysis of the global genome expression of plants chronically exposed to 50 uM of Cd and Pb revealed 65 and 338 up- and down-regulated genes by Cd and 19 and 76 by Pb, respectively. Interestingly, half of the genes that changed their expression in Pb-treated plants also changed their expression in Cd-treated ones. The greater number of genes regulated by Cd reflects generally higher genome instability of plants as well as higher uptake as compared to Pb.