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Background To investigate the association between single nucleotide polymorphisms (SNPs) of PDCD1, CD274, and HAVCR2 genes with the risk and outcomes of non-small cell lung cancer (NSCLC) subtypes: squamous cell lung cancer (LUSC) and lung adenocarcinoma (LUAD). Methods TaqMan SNP genotyping assays or polymerase chain reaction-restriction fragment length polymorphism methods were used to determine genotypes of: PDCD1: rs36084323, rs7421861, rs11568821, rs2227981, rs10204525; CD274: rs822335, rs10815225, rs17718883, rs2297136, rs4742098, rs4143815; HAVCR2: rs10057302, rs1036199. Among 383 NSCLC patients, 112 were diagnosed with LUAD and 116 with LUSC. The control group consisted of 433 unrelated, cancer-free subjects. Results A CC genotype of rs4143815 and GG genotype of rs4742098 were associated with two times higher risk of developing LUSC (CC vs. GG + GC, OR = 2.31; 95% CI = 1.32, 4.06; P = 0.003; GG vs. AA + AG, OR = 2.26; 95% CI = 1.17, 4.36; P = 0.016, respectively). Moreover, rs4143815 was an independent predictor of the age at diagnosis of LUAD. The carriers of C allele were diagnosed 4.81 years later (95% CI = 1.47, 8.15; P = 0.006) than patients with the GG genotype. The rs10057302 CA genotype was an independent predictor of overall survival in LUSC (adjusted HR = 0.13; 95% CI = 0.02, 0.93; P = 0.043). NSCLC carriers of rs11568821 T allele had almost double the risk of death (adjusted HR = 2.05; 95% CI = 1.28, 3.29; P = 0.003) compared to carriers of CC genotype. Conclusions Our results provided additional evidence that SNPs of genes for PD-1, PD-L1 and TIM-3 differentially modulate the risk and prognosis of LUSC and LUAD.

Alterations in circulating Cu and Zn are negative predictors of survival in neoplastic patients and are known during lung cancer. However, no data on predicting mortality of lung cancer patients based on the level of these elements in the blood have been presented to date. The aims of this prospective cohort study were as follows: (i) To evaluate the disturbances in serum and whole blood Cu and Zn, (ii) to assess the relationships between serum and whole blood Cu and Zn status and clinical, sociodemographic, and nutritional data, and (iii) to investigate the association of Cu and Zn status with all-cause mortality in lung cancer. Na&iuml, ve-treatment lung cancer patients (n = 167) were characterized in terms of sociodemographic, clinical, and anthropometric data and dietary intake and compared with sex-matched control subjects (n = 48). Whole blood and serum Cu and Zn status was determined by atomic absorption spectrometry. Cox proportional hazards models adjusted for multiple confounders/mediators were used to estimate the association between all-cause death and Cu and Zn status. Sex, cardiovascular disease, chronic obstructive pulmonary disease, clinical stage, and hemoglobin, platelet, and glucose concentrations significantly differentiated Cu and Zn status. All-cause mortality in lung cancer patients was positively associated with serum Cu levels, Cu:Zn ratio, and whole blood Zn levels. However, an advanced clinical stage of disease was the strongest predictor of all-cause mortality. Circulatory status of Cu and Zn might be included in routine clinical characteristics of patients with lung cancer patients as additional prognostic variables, but only after further more detail studies.

Background A low glycemic index (GI) and glycemic load (GL) of diets as well as proper nutritional status may partially slow down depletion in antioxidant capacity, and may therefore have an impact on antioxidant/ oxidant status in lung cancer patients. However, no studies concerning these associations had previously been conducted. Objectives The aim of this study was to investigate the association between GI or GL and nutritional status and antioxidant/oxidant status in lung cancer patients. Material and methods The study was conducted among 180 lung cancer patients (82 women and 98 men) and 171 control subjects (78 women and 93 men). Exclusion criteria for the control subjects included cancers, pro-inflammatory conditions, brain diseases, and psychiatric disorders. All participants were evaluated in terms of their systemic antioxidant/oxidant status, nutritional status (anthropometric parameters), dietary GI and GL and parameters related to circulating glucose: fasting glucose, insulin level and homeostasis model assessment for insulin resistance (HOMA-IR). Results In women who were lung cancer-positive, associations were observed between total antioxidant status (TAS) and parameters of nutritional status, and between oxidative stress index (OSI) and fasting glucose. In men with lung cancer, we found a positive correlation between total oxidant status (TOS) and GI. In the control group of women, TAS positively correlated with anthropometric parameters, but negatively with dietary fiber and total carbohydrate content. Additionally, TOS and OSI negatively correlated with parameters related to body weight and positively with insulin. In control men, we observed significant negative correlations between parameters related to fasting glucose and TAS and positive ones with TOS and OSI. Conclusions The results show that in lung cancer oxidative stress is related to GI, while TAS is related to nutritional status. Further investigations performed on a larger cohort are required to better clarify the observed relationships as well as to explain the potential mechanisms involved.

Lung cancer is strongly associated with cigarette smoking; nevertheless some never-smokers develop cancer. Immune eradication of cancer cells is dependent on polymorphisms of HLA class I molecules and antigen-processing machinery (APM) components. We have already published highly significant associations of single nucleotide polymorphisms (SNPs) of the ERAP1 gene with non-small cell lung cancer (NSCLC) in Chinese, but not in Polish populations. However, the smoking status of participants was not known in the previous study. Here, we compared the distribution of APM polymorphic variants in larger cohorts of Polish patients with NSCLC and controls, stratified according to their smoking status. We found significant but opposite associations in never-smokers and in smokers of all tested SNPs (rs26653, rs2287987, rs30187, and rs27044) but one (rs26618) in ERAP1. No significant associations were seen in other genes. Haplotype analysis indicated that the distribution of many ERAP1/2 haplotypes is opposite, depending on smoking status. Additionally, haplotypic combination of low activity ERAP1 and the lack of an active form of ERAP2 seems to favor the disease in never-smokers. We also revealed interesting associations of some APM polymorphisms with: age at diagnosis (ERAP1 rs26653), disease stage (ERAP1 rs27044, PSMB9 rs17587), overall survival (ERAP1 rs30187), and response to chemotherapy (ERAP1 rs27044). The results presented here may suggest the important role for ERAP1 in the anti-cancer response, which is different in smokers versus never-smokers, depending to some extent on the presence of ERAP2, and affecting NSCLC clinical course.

Disturbed redox status may be critical to lung cancerogenesis, however little research has been conducted on general changes in total redox status in lung cancer. Levels and activities of antioxidants, especially enzymatic ones, are related to trace element concentration. Trace element status is often disturbed in cancers, however no studies concerning the association between redox and trace element status have been performed for lung cancer. We hypothesized that disturbed redox status in lung cancer patients is partially determined by trace elements while their distribution amongst blood compartments may differ compared to healthy subjects. Blood samples from lung cancer patients (n=44) and control subjects (n=44) were collected to assess redox and trace element status. Serum and whole blood Cu and Mn levels were determined with GF-AAS, and Zn-with F-AAS. In serum the total antioxidant status (TAS) was determined with the commercial kit TAS (Randox, UK), total oxidant status (TOS) was determined based on the method developed by Erel and the oxidative stress index (OSI) was calculated. Total protein (T-Prot), albumin (Alb), uric acid (UA) and total bilirubin (T-Bil) concentrations were measured with an auto-analyser (Konelab 20i, Thermoscientific, USA), SOD and CAT activity - with commercially available kits (Cayman, USA). The level of TAS, T-Prot, Alb, T-Bil, the activity of SOD, the concentration of whole blood Mn as well as serum and whole blood Zn were lower while TOS, OSI, serum Cu levels and serum Cu:Zn ratios were higher in lung cancer patients compared to the control group. In the lung cancer group TAS correlated positively with Alb and UA, serum Zn and negatively with whole blood Mn. Additionally, SOD positively correlated with the whole blood Mn and Cu:Zn ratio, while CAT - negatively with the whole blood Cu:Zn ratio. In the lung cancer sub-group at clinical stage I-II, TOS additionally negatively correlated with whole blood Zn, and CAT negatively with serum Cu and Cu:Zn ratio. In advanced lung cancer, we found a positive correlation between TAS and serum Zn, and a negative one - with serum Cu:Zn ratio. We observed a similar correlation between endogenous non-enzymatic antioxidants and TAS in the control group, however considerably fewer correlations between trace elements and antioxidants were observed. This study supports the hypothesis that disturbed redox status in lung cancer patients is linked with alterations in trace element status regarding Zn, Mn and Cu. Moreover, the type of biological fluid influences both - alterations in the metal profile and relationships with redox status parameters.

BACKGROUND Anemia and malnutrition are frequently observed during lung cancer development, and the associations between them have been researched. However, no study concerning the utility of routinely used nutritional screening tools in predicting anemia in lung cancer has been performed. OBJECTIVES The aim of this study was to assess the usefulness of routinely used malnutrition screening tools in predicting anemia in lung cancer patients. MATERIAL AND METHODS Eighty-five male patients were recruited to this study. Blood counts, serum iron concentration, total iron binding capacity (TIBC) and serum transferrin saturation (STS), measurements of selected anthropometric parameters, Mini Nutritional Assessment (MNA) and Glasgow Prognostic Score (GPS) were performed for the subjects. To evaluate the differences in the distribution of hematological and iron status parameters according to nutritional status, a t-test (Mann-Whitney U test for non-parametric data) and an analysis of variance (ANOVA) were performed. Tukey's post hoc test was performed for intergroup comparison of parametric data. The sensitivity, specificity, positive and negative predictive values of MNA and GPS were compared to blood counts and biochemical parameters of iron status. RESULTS Using the MNA test, we observed that ca. 60% of subjects had deteriorated nutritional status. About half of the patients had inflammation cumulated with malnutrition. A similar part of the subjects had anemia. The MNA test showed a significant difference in the distribution of Hb and Htc, while GPS showed the distribution of Fe and TIBC among lung cancer patients. We did not observe any influence of fat-free mass index (FFMI) on hematological and iron status parameters. The MNA test had very high specificity and positive predictive values (PPV) for all the hematological parameters evaluated as well as GPS for serum Fe concentration and TIBC. CONCLUSIONS Our data demonstrates that an evaluation of nutritional status with the MNA test can provide additional predictive information regarding anemia, while GPS may do the same with type of anemia in lung cancer patients.

Daytime sleepiness is a common symptom among hypertensive patients. The aim of this study was to determine subjective sleepiness assessed by Epworth Sleepiness Scale (ESS) and to asses sleep architecture in 304 patients with arterial hypertension. All patients underwent a standardized diagnostic overnight, polysomnography. The control group consisted of 67 normotensives. The hypertensive patients had a decreased sleep efficiency, mean and minimum oxygen saturation levels, and increased apnea/hypopnea index and oxygen desaturation index compared with normotensive patients. The lower ratio of N3 sleep, higher of N2 sleep, and decreased sleep efficiency was observed in hypertensives without obstructive sleep apnea (OSA). In the moderate to severe OSA groups, the total ESS score was significantly lower in hypertensives compared with normotensives. The ESS scores decreased with age in hypertensives, but not in normotensives. The study showed that ESS total score is lower in hypertensives than in normotensives with OSA, making the OSA more difficult to suspect. Thus, the low ESS score in hypertensives should not discourage further evaluation.

Introduction: Osteoprotegerin (OPG) is a member of the tumor necrosis factor family and a key regulator in bone turnover; it plays a role in the development of many cardiovascular diseases and may be treated as a marker of vascular damage. Bioelectrical impedance analysis (BIA) is a reliable, non-invasive and effective technique for measuring body composition.The aim of the study was to evaluate correlations between osteoprotegerin serum levels and body composition parameters in sleep apnea patients and their influence on cardiovascular risk. Material and methods: A total of 125 patients with newly diagnosed OSA were enrolled in the study (including 34 females). The mean age was 54.48 ± 8.81 years, mean AHI 33.16 ± 20.44/h and mean BMI 33.76 ± 7.18. A control group comprised 59 healthy subjects with mean age of 51.27 ± 12.97 years and mean BMI 29.47 ± 5.42.All subjects underwent a nocturnal respiratory polygraphy and body composition measurements were taken with bioelectrical impedance analysis. OPG serum levels were measured using the enzyme-linked immunosorbent assay (ELISA) method. Results: In OSA patients OPG correlated negatively with muscle mass percentage (MM%), phase angle, fat free mass percentage (FFM%) and body cell mass percentage (BCM%), while there was a positive correlation between osteoprotegerin and fat mass percentage (FM%). We demonstrated higher OPG serum levels in OSA patients with cardiovascular diseases than in those without comorbidities (4.01 vs 3.46 pmol/l, p

Altered systemic redox status is often observed in lung cancer. However, detailed information on factors other, than smoking, which influence this perturbation is rather scarce. Elevated oxidative stress has been linked with disturbances in glucose metabolism before, but such associations have not been investigated in lung cancer. The aim of this study was to evaluate the relationship between systemic parameters of glucose metabolism and redox status in lung cancer patients (LC). Biochemical variables related to circulating glucose, i.e. glucose, insulin, c-peptide, fructosamine (FA), and glucose metabolism, i.e. β-hydroxybutyrate (BHB), lactate (LACT), non-esterified fatty acids (NEFAs), as well as redox status i.e. total antioxidant status (TAS) and total oxidant status (TOS) were determined for LC (n = 122) and control subjects (CS) (n = 84). HOMA-IR and the oxidative stress index (OSI) were calculated. LC patients had an altered redox status and glucose metabolism compared to CS. Positive correlations in LC were observed between TOS, OSI and circulating glucose as well as FA, while TAS positively correlated with BHB and NEFAs. In contrast, in metastatic LC, NEFAs and BHB positively correlated with OSI. Smoking status additionally stratified the observed relationships. In conclusion, we found that parameters related to circulating glucose or non-enzymatic glycation were correlated with oxidative stress (TOS and OSI), while metabolites such as BHB and NEFAs were correlated with antioxidant capacity (TAS). Metastasis prevalence and smoking seem to influence these correlations. However, the detailed mechanism of this relationship requires further research, in particular as regards the surprising positive correlation between NEFAs and TAS.

Aim of the study Assessment of lung cancer patients’ dietary habits before treatment enable medical staff to provide more individual, precise and complex care to patients, taking into consideration their nutritional status. The aim of this study was, therefore, to evaluate dietary habits related to lung cancer risk of lung cancer patients in comparison with controls from the Lower Silesia region of Poland. Material and methods Assessments of dietary habits, based on a validated questionnaire related to lung cancer risk were performed on 92 lung cancer patients and compared with the results obtained in 157 controls. Dietary patterns were evaluated concerning on eating frequency of high- and low- glycemic index products, vegetables and fruits, vegetable and fruit juices, green tea, liquid dairy products, meat and fried products over the previous year. Alcohol consumption was assessed on a dichotomous scale (yes or no). Results Majority of patients had inappropriate dietary habits, such as low consumption of low GI cereal products, vegetables, fruit and green tea, and a high consumption frequency of fried products. Conclusions Reported dietary mistakes indicate the need for dietary education among people at lung cancer risk and with newly diagnosed disease, to enhance their nutritional status.

Year after year, a growing number of cases of non-small cell lung cancer (NSCLC), mostly caused by smoking, have been noted. Most patients die because of the late detection of cancer and tumor resistance to treatment with cytostatics. Treatment of patients with advanced NSCLC is impeded by the low sensitivity of the tumor to cytostatic agents and the co-existence of many diseases, which substrate is, like lung cancer, cigarette smoking. Along with the development of molecular biology, targeted therapy has started to be used, affecting specific signaling pathways involved in the processes of oncogenesis. Compounds that inhibit the activity of receptor tyrosine kinases are very well examined and already used in clinical practice. NSCLC is characterized by multiple mutations, including EGFR (epidermal growth factor receptor) and KRAS. Rarer but clinically significant is the rearrangement of the ALK gene. Currently, for NSCLC treatment a number of EGFR inhibitors such as erlotinib, gefitinib, afatinib and two compounds targeted in ALK kinase crizotinib and ceritinib are applied. Unfortunately, despite numerous studies, we are still not able to improve the treatment effectiveness of patients with KRAS mutations. The most efficient solution would be to use a combination of the compounds exhibiting synergistic effects on tumor cells. The literature data describes numerous examples of the combination treatment of NSCLC cells. Some combinations of compounds are already in clinical trials. Most attempts relate to tyrosine kinase inhibitors in combination with other types of pharmacologic inhibitor or immunotherapy. This paper describes the mutations occurring in NSCLC and drugs used in clinical practice as well as being in preclinical development.

Chronic obstructive pulmonary disease (COPD) and lung cancer are widespread lung diseases. Cigarette smoking is a high risk factor for both the diseases. COPD may increase the risk of developing lung cancer. Thus, it is crucial to be able to distinguish between these two pathological states, especially considering the early stages of lung cancer. Novel diagnostic and monitoring tools are required to properly determine lung cancer progression because this information directly impacts the type of the treatment prescribed. In this study, serum samples collected from 22 COPD and 77 lung cancer (TNM stages I, II, III, and IV) patients were analyzed. Then, a collection of NMR metabolic fingerprints was modeled using discriminant orthogonal partial least squares regression (OPLS-DA) and further interpreted by univariate statistics. The constructed discriminant models helped to successfully distinguish between the metabolic fingerprints of COPD and lung cancer patients (AUC training=0.972, AUC test=0.993), COPD and early lung cancer patients (AUC training=1.000, AUC test=1.000), and COPD and advanced lung cancer patients (AUC training=0.983, AUC test=1.000). Decreased acetate, citrate, and methanol levels together with the increased N-acetylated glycoproteins, leucine, lysine, mannose, choline, and lipid (CH3-(CH2)n-) levels were observed in all lung cancer patients compared with the COPD group. The evaluation of lung cancer progression was also successful using OPLS-DA (AUC training=0.811, AUC test=0.904). Based on the results, the following metabolite biomarkers may prove useful in distinguishing lung cancer states: isoleucine, acetoacetate, and creatine as well as the two NMR signals of N-acetylated glycoproteins and glycerol.

The aim of this paper was to assess dietary intake and characterize the sociodemographic and smoking status ina lungcancerpatientgroup. Material and methods: The research was performed among 15 women and 29 men who carried out a questionnaire of sociodemographic status and 24-h dietary recall from the last three days before hospitalisation. Obtained results were compared with Polish RDA (Rec ommended Dietary Allowances) and references. Results: Every third person of all respon dents had a vocational education; a sim ilar percentage of patients were prima ry educated. All subjects were current or former smokers. Intake of fat and saturated fatty acids was higher than RDA and there were found deficiencies of polyunsaturated fatty acids and car bohydrates. The average diet of men and women provides copper and zinc below the relevant RDA. Only the aver age mean daily supply of sodium and phosphorus in meals of patients exceeded RDA of these minerals. The mean intake of antioxidant vitamins with diets was too high while the mean amount of B group vitamins in diets was lower than RDA. Conclusion: Incorrect dietary habits demonstrated in patients during the period before lung cancer diagnosis in combination with smoking and low education could contribute to the development of lung cancer.

Obstructive sleep apnea (OSA) is a common respiratory disorder associated with hypertension and cardiovascular complications. Blood pressure variability may be a sign of risk of cardiovascular events. The aim of this study was to investigate the hypothesis that severe OSA syndrome is associated with increased blood pressure variability. Based on respiratory polygraphy, 58 patients were categorized into two groups: severe OSA with apnea/hypopnea index (AHI) greater than 29 episodes per hour (mean 52.2 ± 19.0/h) and mild-to-moderate OSA with AHI between 5 and 30 episodes per hour (mean 20.2 ± 7.8/h). A 24-h noninvasive blood pressure monitoring was performed. The standard deviation of mean blood pressure was used as the indicator of blood pressure variability. In patients with severe, compared with mild-to-moderate OSA, a higher mean nocturnal systolic blood pressure (133.2 ± 17.4 mmHg vs. 117.7 ± 31.2 mmHg, p < 0.05) and diastolic blood pressure (80.9 ± 13.1 mmHg vs. 73.8 ± 9.2, p < 0.01), nocturnal systolic blood pressure variability (12.1 ± 6.0 vs. 7.6 ± 4.3, p < 0.01) and diastolic blood pressure variability (10.5 ± 6.1 vs. 7.3 ± 4.0 p < 0.05), nocturnal mean blood pressure variability (9.1 ± 4.9 mmHg vs. 6.8 ± 3.5 mmHg) were detected. The findings of the study point to increased nocturnal systolic and diastolic arterial blood pressure and blood pressure variability as risk factors of cardiovascular complications in patients with severe OSA.

Introduction: Taking into account important role of apoptosis in COPD pathogenesis, we wanted to asses the serum levels of markers involved in apoptosis regulation, including apoptosis inducers such as TNF-α, sFasL or p53 protein and apoptosis inhibitor bcl-2 and, in addition, to compare these markers with selected COPD parameters. Material and methods: In 181 patients (60 women) with COPD (age was 62.2 + 9.37 years; FEV1% 55.2 + 19.98 %) and in 29 controls (11 women), serum levels of TNF-α, sFasL, p53 and bcl-2 were evaluated by the enzyme-linked immunosorbent assay (ELISA) method. Results: In COPD patients the mean sFasL level was 0.092 ± 0.077 ng/mL and mean TNF-α level was 2.911 ± 3.239 pg/mL. There were no differences in serum sFasL and TNF-α in COPD patients and control group. TNF-α and sFasL did not correlate with COPD parameters such as FEV1%, BMI, RV% (percentage of predicted value of residual volume) or BODE. Although we tried to evaluate bcl-2 and p53 protein serum levels with two different tests, measurable levels of bcl-2 were only detected in 15 patients and p53 in only 3 patients. Bcl-2 values were from 0.418 to 11.423 ng/mL and p53 from 90.772 to 994.749 pg/mL. Conclusions: We didn’t observe any differences in serum levels of pro- and antiapoptotic markers in COPD patients and the control group or correlations between the markers studied and COPD parameters.

Aim of the study: In the paper clinical cases of individuals diagnosed with lung cancer below the age of 40 years have been analyzed. Material and methods: The analysis included: sex, age, clinical symptoms found before and at the moment of diag nosis, character of changes visible in radi ological imaging, time that passed from the first symptoms to reporting to a doc tor and to establishing a diagnosis, type of diagnostic method used in establish ing the final diagnosis, histopathologic type of cancer, degree of cancer pro gression. Results: The results have been compared with a peer group who had been diag nosed 20 years earlier. Currently 7% of patients were diagnosed at the age of 25 or younger, whereas in the previous cohort patients in this age constituted 2%. The predominant pathological type was adenocarcinoma (currently 33%, previously 4%) in contrast to the earli er group in which 57% of patients had small cell lung cancer (57%). The inci dence is equally distributed between both sexes, although there is an evident increase in female lung cancer cases. In the majority of patients the clinical pre sentation is a peripheral mass on chest X-ray. 20% of patients present pleural effusion on diagnosis. Patients reported the following complaints: breathlessness, chest pain, weight loss and fatigue. The majority of cases were diagnosed in advanced stages on the basis of a bron choscopy acquired specimen. Time course from symptoms to diagnosis tends to be shorter than 20 years ago.

Sclerostin, a glycoprotein involved in vascular calcification, could play a role in cardiovascular disorders. Obstructive sleep apnea (OSA) is frequently associated with cardiovascular comorbidities. Thus, in this study we set out to assess the level of sclerostin in patients with OSA. Sclerostin was evaluated in the serum by ELISA method in 106 patients (43 women) with OSA of the mean age of 55 ± 10 years, BMI of 33.1 ± 7.9 kg/m2, and apnea/hypopnea index (AHI) of 29.7 ± 18.9. There were 76 (72 %) patients with cardiovascular comorbidities in the OSA group. The results were compared with those in 49 healthy control subjects. We found that the level of sclerostin was higher in the female OSA patients than that in female controls (80.1 ± 36.5 pg/ml vs. 61.4 ± 24.1 pg/ml; p < 0.05) and it correlated with AHI (rs = 0.32, p < 0.01) and desaturation index (rs = 0.34, p < 0.01). Further, in OSA women with cardiovascular comorbidities, sclerostin was higher than in women without such comorbidities (87.0 ± 37.4 pg/ml vs. 57.3 ± 22.1 pg/ml; p < 0.05). In men, there were no differences in the serum sclerostin level between the OSA and control subjects, nor was there any relationship with cardiovascular diseases. In conclusion, increased serum sclerostin coincides with the severity of OSA and its cardiovascular sequelae in female patients.

Lung cancer is still an oncology challenge. A 5-year survival reaches less than 20 % of patients. Apoptosis disturbances are a key step in cancer development. The evaluation of apoptosis markers has a great potential in lung cancer. The goal of our study was a comparative evaluation of apoptosis regulators: p53, Bcl-2, Bax, COX-2, and survivin in lung adenocarcinoma (AC) and squamous cell carcinoma (SCC). We also evaluated the relationship between apoptosis markers and clinicopathological parameters. Fifty six patients with non-small cell lung cancer (NSCLC) were included into the study (20 women and 36 men). AC was diagnosed in 30 and SCC in 26 cases. The evaluation of markers was performed using an immunohistochemical method on paraffin embedded tissue specimens. We used monoclonal antibodies for p53, bcl-2, and COX2-proteins (clone DO7, bcl-2/100/D5, and 4H12, respectively), Bax (B-9 clone) and survivin (clone 12C4). The results of immunostaining were viewed by light microscopy. We revealed significantly more frequent expression of Bax and survivin in lung AC than SCC (p < 0.01 and p < 0.019). Bcl-2 immunoreactivity was seen more often in AC without lymph node metastases than with metastases (p = 0.046). There was no correlation between the apoptosis markers and gender or the presence of vessel emboli. A greater variability in markers expression was seen in lung AC than SCC. There were significant differences in the Bax and survivin expression in the two major pathological types of NSCLC. We did not revealed any correlation between the markers and TNM characteristics, accept for Bcl-2 presence along with the lymph node involvement in the AC group.

The overexpression of three growth factor receptors: epidermal growth factor receptor (EGFR), ERB B2 and ERB B3 was evaluated immunohistochemically in 77 malignant and 15 benign colorectal neoplasms considering clinicopathological variables (histological structure, grade of differentiation, tumor localization, clinical stage of the disease). The relationship between the coexpression of EGFR-related proteins in individual patients was also evaluated. EGFR expression was revealed in comparable percentages of colorectal adenoma and in adenocarcinoma cases (80% and 70%) while ERB B2 expression was detectable more frequently in adenoma than in adenocarcinoma cases (87% and 54%). The presence of ERB B3 was observed in a higher percentage of adenocarcinoma than adenoma cases (65% and 40%). There was no correlation between the expression of studied tyrosine kinase receptors and histological grade or Dukes' clinical stage and localization (proximal or distal) of colorectal adenocarcinoma. The incidence of EGFR and ERB B2 expression was higher in tubulovillous (100% for both receptors) than in tubular adenomas (63% and 75%), while the ERB B3 receptor was revealed more frequently in tubular than in tubulovillous neoplasms (50% and 28%). These differences appeared to be statistically nonsignificant. The concomitant expression of two growth factor receptors was observed in a higher percentage of colorectal adenomas than adenocarcinomas, and the coexistence of three growth factors was revealed in comparable percentages in malignant and benign colorectal tumors. Our results support the promotional rather than direct transformational role for the EGFR supergene family in colorectal tumorigenesis. The frequently observed coexpression of more than one EGFR-related protein in colorectal neoplasms indicates the possible cooperation of these receptors in mitogenic signaling transduction, facilitating the development and maintenance of the malignant phenotype.

SDS-agarose FN immunoblotting of 257 normal and pathological human plasma samples revealed the ladder pattern of multiple plasma FN bands which corresponded to FN monomer and dimer, and 5 FN-fibrin bands with increasing molecular masses. The FN-fibrin bands of about 750 kDa, 1000 kDa, 1300 kDa, 1600 kDa, and 1900 kDa appeared more frequently and in significantly higher relative amounts in the pathological samples (P < 0.000) than in relatively healthy individuals. The revealing of high-molecular FN-fibrin complexes by SDS-agarose FN immunobloting might have the potential to become a laboratory biomarker of some diseases in which the coagulation system is triggered.

Wstęp: Proces apoptozy może odgrywać ważną rolę w patogenezie przewlekłej obturacyjnej choroby płuc (POChP). Autorzy ocenili stężenie markerów związanych z regulacja apoptozy, w tym markerów indukujących apoptozę—TNF-α, sFasL i białka p53 oraz hamujących apoptozę—bcl-2. Ponadto w pracy oceniono związek pomiędzy badanymi markerami a parametrami klinicznymi POChP. Materiał i metody: Do grupy badanej włączono 181 chorych na POChP (60 kobiet, wiek 62.2 ± 9.37 lat, FEV1% 55.2 ± 19.98%), grupa kontrolna złożona była z 29 osób (11 kobiet). Stężenia TNF-α, sFasL, p53 i bcl-2 w surowicy oznaczono metodą ELISA (enzyme-linked immunosorbent assay). Wyniki: Średnie stężenie sFasL w surowicy chorych na POChP wynosiło 0.092 ± 0.077 ng/mL, a stężenie TNF-α 2.911 ± 3.239 pg/mL. Stężenia w grupie chorych i grupie kontrolnej nie różniły się, nie stwierdzono również korelacji pomiędzy badanymi markerami a parametrami klinicznymi, takimi jak FEV1%, BMI, RV% (objętość zalegająca w % wartości należnej) oraz wskaźnikiem BODE. Mimo użycia dwóch różnych metod diagnostycznych stężenie bcl-2 przekraczało poziom detekcji u 15 chorych, a stężenie p53 było wyższe od progu detekcji zaledwie u 3 chorych. Stężenia bcl-2 wahały się od 0.418 do 11.423 ng/mL a p53 od 90.772 do 994.749 pg/mL. Wnioski: Nie stwierdzono różnic w stężeniach markerów pro- i anty-apoptotycznych pomiędzy grupą chorych na POChP i grupą kontrolną. Stężenia badanych markerów nie korelowały z parametrami klinicznymi.

Both obstructive sleep apnea (OSA) syndrome and chronic obstructive pulmonary disease (COPD) may lead to chronic alveolar hypoventilation. The coexistence of OSA syndrome and COPD has been named the overlap syndrome. The aim of the study was to elucidate the relationship between the severity of COPD and the occurrence of chronic alveolar hypoventilation in patients with OSA syndrome.The material of the study consisted of 64 obese (BMI 40 ± 5.5 kg/m(2)) patients with OSA syndrome (AHI 〉15, mean 52 ± 23) and coexisting COPD (FEV1/FVC 〈 70%). The results of polysomnographic, spirometric and arterial blood gases studies have been evaluated.Chronic alveolar hypoventilation has been found in 67% of the patients: in 60.5% of patients in the spirometric stage II, in 85% of patients in the stage III and in all the patients in the stage IV of COPD. In the patients with chronic alveolar hypoventilation as compared with the remaining patiens there were: lower FVC (2.7 ± 0.8 L v. 3.6 ± 0.9 L; p 〈 0.001), FEV(1) (1.7 ± 0.6 L v. 2.2 ± 0.5 L; p 〈 0.001) and mean SaO(2) during obstructive sleep apneas and hypopneas (75 ± 10% v. 84 ± 5%; p 〈 0.001).Chronic alveolar hypoventilation occurs in most of the obese patients with moderate and severe OSA syndrome and coexisting COPD, including most of the patients with moderately impaired ventilatory function. The occurrence of chronic alveolar hypoventilation in the course of the overlap syndrome is related to the restrictive ventilatory pattern and the lower mean and minimal SaO(2) during obstructive sleep apneas and hypopneas.

Background: Obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) may lead to chronic alveolar hypoventilation. The coexistence of OSA and COPD has been termed the ‘overlap syndrome’. The aim of the study was to determine the relationship between the severity of COPD and the occurrence of chronic alveolar hypoventilation in patients with OSA and to evaluate the impact of chronic alveolar hypoventilation in patients with the overlap syndrome on the severity of breathing disorders during sleep. Material and methods: The study included 64 obese patients (BMI 40.0 ± 6.5 kg/m2) with OSA (AHI > 15; mean AHI 52 ± 22) coexisting with COPD. We analysed the results of polysomnography, spirometry and arterial blood gas analysis. Results: Chronic alveolar hypoventilation was present in 67% of the patients, including 60.5%, 85% and 100% of patients with moderate, severe and very severe COPD by spirometry, respectively. Patients with chronic alveolar hypoventilation had lower values of FVC (2.7 ± 0.8 l vs. 3.6 ± 0.9 l; p < 0.001), FEV1 (1.7 ± 0.6 l vs. 2.2 ± 0.5 l; p < 0.001) and mean SaO2 at the end of obstructive sleep apneas and hypopneas (75% ± 10% vs. 84% ± 5%; p < 0.001). Conclusions: Chronic alveolar hypoventilation is observed in the majority of obese patients with moderate to severe OSA and coexisting COPD, including moderate COPD. The occurrence of chronic alveolar hypoventilation in obese patients with OSA coexisting with COPD is associated with a marked arterial hypoxia during obstructive sleep apneic and hypopneic episodes.

An effective cytotoxic immune response to neoplastic cells requires efficient presentation of antigenic peptides to T lymphocytes by HLA class I (HLA-I) molecules. The HLA-I-bound peptide repertoire depends on antigen-processing machinery molecules. Aminopeptidase residing in endoplasmic reticulum 1 (ERAP1) trims peptides to the optimal length for HLA-I binding. Single nucleotide polymorphisms (SNPs) in the ERAP1 gene result in changes in aminopeptidase activity and specificity. This may affect susceptibility to cancer. However, non-small cell lung carcinoma (NSCLC) has not been studied in this respect. We compared genotype and haplotype frequencies of four coding, nonsynonymous ERAP1 SNPs, rs26653G > C, rs26618T > C, rs30187C > T, and rs27044C > G, in NSCLC occurring in two genetically distant populations, Chinese and Poles. We found associations of all four SNPs with NSCLC in Chinese but not in Poles. The differences in ERAP1-NSCLC associations might be explained by highly significant differences in SNP genotype frequencies between Chinese and Poles (except for rs26618). In accordance with this, the most frequent ERAP1 haplotypes were distributed differently in cases versus controls in Chinese, but not in Poles. Our findings add to the differences between Orientals and Caucasians in genetics of disease susceptibility. Electronic supplementary material The online version of this article (doi:10.1007/s00005-016-0436-4) contains supplementary material, which is available to authorized users.