Decreased sL-selectin serum levels in sleep apnea syndrome patients with cardiovascular diseases.

BACKGROUND: Obstructive sleep apnea syndrome (OSA) is a common disorder associated with an increased risk of cardiovascular diseases. OBJECTIVES: sL-selectin is an adhesion molecule released from the surface of leukocytes as they are activated and may inhibit leukocyte attachment to the endothelium. The aim of this study was to evaluate sL-selectin serum levels in OSA patients with cardiovascular diseases. MATERIAL AND METHODS: A total of 163 OSA patients were enrolled in the study. The mean age was 55.41 ± 8.63 years and the mean AHI (apnea hypopnea index) was 35.02 ± 22.28/h. A control group was composed of 59 healthy subjects. All subjects underwent a nocturnal respiratory polygraphy. sL-selectin serum levels were measured using the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: sL-selectin serum levels were significantly lower in OSA patients than in the control group (1080.02 ± 175.29 vs 1350.73 ± 569.75 ng/mL, p < 0.05). In addition, there was a negative correlation between sL-selectin levels and AHI and DI and a positive correlation between sL-selectin levels and mean and minimum saturation. sL-selectin levels were lower in OSA patients with cardiovascular diseases than in those without co-morbidities. We also found that sL-selectin correlated positively with HDL-cholesterol (high density lipoprotein) and negatively with uric acid and CRP (C-reactive protein). CONCLUSIONS: Our work, together with observations relating to other diseases and experimental studies, suggests that lower sL-selectin levels could play a role in an increased risk of cardiovascular complications in sleep apnea syndrome. However future studies are needed to understand the role of sL-selectin in sleep apnea syndrome.

Serum levels of apoptosis-related markers (sFasL, TNF-a, p53 and bcl-2) in COPD patients.

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-a, 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-a, 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-a level was 2.911 ± 3.239 pg/ml. There were no differences in serum sFasL and TNF-a in COPD patients and control group. TNF-a 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.

Human leukocyte antigen (HLA)-G gene polymorphism in patients with non-small cell lung cancer.

BACKGROUND: Lung cancer represents the highest morbidity and mortality caused by neoplasms in the world; therefore researchers continue to search for new tools to diagnose and treat the disease. The aim of the study was to establish the role of single nucleotide polymorphisms (SNP) in the promoter region of the human leukocyte antigen (HLA)-G gene in patients with non-small cell lung cancer. METHODS: We enrolled 143 patients with a mean age of 63 years, diagnosed with non-small cell lung cancer, in the study. Adenocarcinomas made up 33% of the cases. Patients in stage III or IV of the tumor node metastasis staging system made up 59%. Two polymorphic sites in the promoter region of the HLA-G gene were genotyped (-725C>G>T and -716T>G). RESULTS: All genotyped SNPs were in Hardy-Weinberg equilibrium. No proof of a relationship between genotype -725C>G>T or -716T>G and the risk of lung cancer compared with healthy volunteers from the literature was found. We also found no correlation between the two SNPs and survival time, histological type of cancer, T stage, the presence of remote metastases or performance status according to the Eastern Cooperative Oncology Group (ECOG) scale. The only association we found was genotype -725C>G>T and the degree of lymph node metastases (N stage). CONCLUSIONS: SNPs of the promoter of the HLA-G gene may have an impact on the development of lymph node metastases. In the study we did not prove a relationship between the examined SNPs and the course of the disease because of the small patient groups studied.

Fusion of the 1H NMR data of serum, urine and exhaled breath condensate in order to discriminate chronic obstructive pulmonary disease and obstructive sleep apnea syndrome.

Chronic obstructive pulmonary disease, COPD, affects the condition of the entire human organism and causes multiple comorbidities. Pathological lung changes lead to quantitative changes in the composition of the metabolites in different body fluids. The obstructive sleep apnea syndrome, OSAS, occurs in conjunction with chronic obstructive pulmonary disease in about 10-20 % of individuals who have COPD. Both conditions share the same comorbidities and this makes differentiating them difficult. The aim of this study was to investigate whether it is possible to diagnose a patient with either COPD or the OSA syndrome using a set of selected metabolites and to determine whether the metabolites that are present in one type of biofluid (serum, exhaled breath condensate or urine) or whether a combination of metabolites that are present in two biofluids or whether a set of metabolites that are present in all three biofluids are necessary to correctly diagnose a patient. A quantitative analysis of the metabolites in all three biofluid samples was performed using 1H NMR spectroscopy. A multivariate bootstrap approach that combines partial least squares regression with the variable importance in projection score (VIP-score) and selectivity ratio (SR) was adopted in order to construct discriminant diagnostic models for the groups of individuals with COPD and OSAS. A comparison study of all of the discriminant models that were constructed and validated showed that the discriminant partial least squares model using only ten urine metabolites (selected with the SR approach) has a specificity of 100 % and a sensitivity of 86.67 %. This model (AUCtest = 0.95) presented the best prediction performance. The main conclusion of this study is that urine metabolites, among the others, present the highest probability for correctly identifying patents with COPD and the lowest probability for an incorrect identification of the OSA syndrome as developed COPD. Another important conclusion is that the changes in the metabolite levels of exhaled breath condensates do not appear to be specific enough to differentiate between patients with COPD and OSAS.

Dietary habits of lung cancer patients from the Lower Silesia region of Poland.

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.

Metabolomics provide new insights on lung cancer staging and discrimination from chronic obstructive pulmonary disease.

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.

[Neurosarcoidosis--case report]. / Neurosarkoidoza--opis przypadku.

Sarcoidosis is a granulomatous disease of unknown cause. It could affect many organs, including nervous system. A forty two years old female patient with neurosarcoidosis is described. The disease began with the lung and thoracic lymph nods involvement. After mediastinoscopy sarcoidosis was histopathologicaly confirmed. A few months after the diagnosis of neurological symptoms appeared in the form of seizure, the vibration of the eyelids and numbness around the mouth. MRI revealed changes in the brain typical for neurosarcoidosis. After corticosteroids treatment excellent recovery was achieved, confirmed in next MRI.

Comparison of haptoglobin and alpha1-acid glycoprotein glycosylation in the sera of small cell and non-small cell lung cancer patients.

INTRODUCTION: Cancer-related carbohydrate epitopes, which are regarded as potential diagnostic and prognostic biomarkers, are carried on the main acute phase proteins. It is not clear, however, if the glycosylation profile is similar in different glycoproteins, or it is protein specific to some extent. The aim of the study was to compare fucosylation, α2,3 sialylation and expression of sialyl-Lewisx epitopes (sLe(x)) in the serum as a whole, AGP and haptoglobin of small cell (SCLC) and non-small cell lung cancer (NSCLC) patients with respect to healthy subjects as well as the cancer stage and its histological type. MATERIAL AND METHODS: Thirty-three NSCLC, 13 SCLC patients and 20 healthy volunteers were included in the study. Carbohydrate epitopes were detected by means of their reactivity with specific lectins and monoclonal anti-sLe(x) antibodies in direct or dual-ligand ELISA tests. RESULTS: Significantly increased fucosylation was found in total serum in both cancer groups and in NSCLC haptoglobin. No difference was observed in SCLC haptoglobin or α1-acid glycoprotein in both cancer groups. Also α2,3 sialylation was elevated in total serum, but not in α1-acid glycoprotein. This type of sialylation was undetectable in haptoglobin by means of MAA reactivity, in both healthy and cancer subjects. Complete sLe(x) antigens were overexpressed in total NSCLC serum and SCLC AGP, and their level was considerably lowered in cancer haptoglobin. DISCUSSION: Typical acute phase proteins, haptoglobin and AGP, exhibit different glycosylation profiles in lung cancer. Alterations observed in haptoglobin reflected the disease process better than those in AGP. Comparison of haptoglobin and AGP glycosylation to that observed in total serum suggests that some efficient carriers of disease-altered glycoproteins still remain unidentified.

Expression of metallothionein-III in patients with non-small cell lung cancer.

BACKGROUND: Currently, there is little knowledge concerning expression of metallothionein-III (MT-III), also known as growth-inhibitory factor, in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: In this study, we evaluated MT-III expression in 184 patients using immunohistochemistry and in 61 cases using real-time polymerase chain reaction. RESULTS: MT-III mRNA expression was significantly higher in NSCLC as compared to non-malignant lung tissues (NMLT; p<0.0086). MT-III expression was noted in the cytoplasm and nucleus of cancer cells. Significantly lower nuclear MT-III (p<0.0001) expression and significantly higher cytoplasmic MT-III (p=0.0068) expression was noted in the pneumocytes of NMLT, as compared to NSCLC. Nuclear MT-III expression was significantly higher in G1 cases as compared to G2 (p=0.0308) and G3 (p=0.0194) cases. Low cytoplasmic MT-III expression was associated with larger primary tumour size (p=0.0378). Lower MT-III mRNA and cytoplasmic MT-III expression was associated with poor patient outcome (p=0.0410 and p=0.0347, respectively). CONCLUSION: MT-III expression may have an impact on the pathogenesis of NSCLC.

Metallothionein 1F and 2A overexpression predicts poor outcome of non-small cell lung cancer patients.

Metallothioneins (MT) are intracellular, low molecular weight proteins (6-7 kDa) involved in binding of metal ions, scavenging of free radicals, cell proliferation and apoptosis and resistance to certain chemotherapeutics. Four basic families of MT proteins are distinguished: MT-I, MT-II, MT-III, MT-IV, within each of them different isoforms occur. The study aimed at examining the expression level of nine MT isoforms: MT-1A, -1B, -1E, -1F, -1G, -1H, -1X, MT-2A and MT-IV by using real-time PCR and MT-I/II expression by immunohistochemical (IHC) technique in 69 cases of non-small cell lung cancer (NSCLC) and 12 non-malignant lung tissues (NMLT) and to correlate them with patients clinicopathological data and Ki-67 antigen expression. Out of all the analyzed cases, 62 (89.9%) demonstrated an increased MT-I/II expression. MT-1B, 1F, -1G, -1H and MT-1X were significantly up-regulated, whereas MT-1E was significantly down-regulated in NSCLC as compared to NMLT. Only in two cases MT-IV mRNA expression was noted. Significant positive correlations were observed between each particular MT isoform expressions. Higher MT-1F and MT-1A mRNA expression was associated with larger primary tumor size (P=0.0362 and P<0.0001, respectively). Moreover, up-regulated MT-1F mRNA expression was associated with higher grade of malignancy of NSCLC (P=0.0085). Higher MT-1B mRNA expression was associated with squamocellular and adenocarcinoma subtype of NSCLC (P=0.0358). Univariate analysis showed, that up-regulated MT-1F and MT-2A mRNA predicted poor patients' survival (P=0.0206 and P=0.0097, respectively). The levels of MT-1F and MT-2A mRNA could be considered as new markers of poor prognosis of NSCLC patients.

Hypoxemia during bilevel positive airway pressure treatment in patients with obstructive sleep apnea syndrome and chronic respiratory insufficiency.

In patients with obstructive sleep apnea (OSA) syndrome and chronic respiratory insufficiency one of the options of treatment is bilevel positive airway pressure (BPAP) during sleep. The aim of the study was to find out what are the factors influencing the early results of BPAP treatment in such OSA patients. The study was carried out in 55 adult obese patients (mean body mass index 45 ± 7 kg/m(2)), severe OSA syndrome (mean apnea/hypopnea index 62 ± 19), and chronic respiratory insufficiency (mean PaCO(2) 54 ± 5.7 torr) who underwent polysomnography during BPAP treatment. In 31 patients (56%) the mean SaO(2) during sleep was <88% despite the optimal BPAP and oxygen titration: 83 ± 4% during NREM and 81 ± 7% during REM sleep vs. 91 ± 2% and 90 ± 3%, respectively, in the remaining 24 patients (p < 0.001). The patients with advanced hypoxemia during sleep and BPAP treatment had lower forced vital capacity (2.2 ± 0.9 vs. 2.7 ± 0.8 l, p < 0.05), lower diurnal PaO(2) (49 ± 8 vs. 54 ± 7 torr), higher diurnal PaCO(2) (57 ± 5 vs. 52 ± 5 torr, p < 0.01), and higher PaCO(2) during sleep (75 ± 13 vs. 59.5 ± 7.5 torr). In conclusion, in obese patients with severe OSA syndrome and chronic alveolar hypoventilation there is a risk of sleep hypoxemia during BPAP treatment, despite optimal pressure titration.

Pulmonary function impairment in patients undergoing allogeneic hematopoietic cell transplantation.

Deterioration of pulmonary function can be the sole symptom of early stages of pulmonary complications following allogeneic hematopoietic cells transplantation (alloHCT). The aim of the study was to evaluate the prevalence and types of pulmonary function abnormalities in allogenic cells recipients. Twenty three (5 children and 18 adults) allogeneic hematopoietic cells recipients who underwent pulmonary function assessment before and 6-12 months after alloHCT were included in the study. Forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC), total lung capacity (TLC), and lung diffusion capacity for carbon dioxide (D(L)CO) were determined. Values <80% of predicted were considered abnormal. We found significant reductions of FVC, D(L)CO, and TLC after alloHCT. The most important reduction was noted in D(L)CO (pre-alloHCT of 85%±15% vs. post- alloHCT of 60% ± 21%, p< 0.05). Six patients (26%) presented with lung function impairment before alloHCT: obstructive lung disease (4%), restrictive lung disease (13%), and decreased D(L)CO (17%). In 19 patients (83%) pulmonary function abnormalities were demonstrated after alloHCT. The most common disturbance was a D(L)CO decrease that occurred in 16 patients (70%). In conclusion, frequency of pulmonary function abnormalities in patients after alloHCT is high. A diffusion capacity decrease and restrictive pattern of ventilation insufficiency develop in the majority of patients after alloHCT. It would be reasonable to include pulmonary function testing to standard periodic examination in patients qualified for, and after, alloHCT procedure.

The evaluation of body composition, adiponectin, C-reactive protein and cholesterol levels in patients with obstructive sleep apnea syndrome.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is a frequent disease, characterized by repetitive episodes of upper airway obstruction during sleep, leading to many pathological events. Adiponectin is an adipocyte-specific secreted protein that plays a role in glucose and lipid homeostasis, in addition to antiatherogenic and anti-diabetic effects. Bioelectrical impedance analysis (BIA) is a reliable, non-invasive, safe and effective technique to measure body composition. OBJECTIVES: The aim of the study was the evaluation of body composition and adiponectin serum levels in OSAS patients and their comparison with OSAS parameters as well as with C-reactive protein (CRP) and cholesterol levels. MATERIAL AND METHODS: In this study, 137 patients with OSAS and 42 persons for the control group were enrolled. In the examined group with OSAS, there were 100 males (73%) and 37 females (27%). The average age was 54.37 + 9.8 years. All subjects underwent polysomnography with Grass Aura PSG Lite and bioelectrical impedance analysis (BIA) with a single-frequency bioimpedance analyzer (Model BIA 101, AKERN-RJL, Italy). The adiponectin serum level was measured using a sandwich ELISA kit. RESULTS: In OSAS patients we demonstrated a higher body mass index (BMI) and percentage of extracellular water (ECW%) and lower percentage of intracellular water (ICW%) and phase angle. Moreover, severe OSAS and control comparison revealed a lower percentage of muscle mass (MM%) in severe OSAS. Positive correlations were found between the apnea-hypopnea index (AHI) and BMI, CRP and ECW%. Negative correlations were observed between AHI and ICW%, MM% and phase angle. We found neither differences in adiponectin levels between the control group and OSAS patients nor correlations between adiponectin and body composition parameters. But we showed that adiponectin levels were significantly lower in OSAS patients with diabetes than in OSAS patients without diabetes (2.64 vs. 13.46 µg/mL, p = 0.003). In OSAS patients without diabetes, we revealed many negative correlations between adiponectin levels and the body composition parameters (including phase angle, percentage of total body water - TBW%, ICW%, percentage of fat free mass - FFM% and MM%) and triglycerides. The positive relationships were between adiponectin and CRP, ECW% and percentage of fat mass (FM%). CONCLUSIONS: Our results indicate that in OSAS patients there are many changes in body composition. The most interesting are higher BMI, TBW% and ECW% and lower BCM%, IW%, MM% and phase angle. Our results suggest that OSAS does not influence adiponectin level, but adiponectin levels are lower in patients with diabetes. Adiponectin levels correlate with many body composition parameters in OSAS patients without diabetes.

KIR2DL2/S2 and HLA-C C1C1 genotype is associated with better response to treatment and prolonged survival of patients with non-small cell lung cancer in a Polish Caucasian population.

Non-small cell lung carcinoma (NSCLC) is a multifactorial disease influenced by both environmental and genetic factors. Here, we examined whether the repertoire of genes encoding killer immunoglobulin-like receptors (KIR) and genes for their ligands, C1/C2 and Bw4, may affect a susceptibility to NSCLC and response to treatment. We typed 269 NSCLC patients and 690 healthy control individuals for KIR genes and for their ligands. KIR genes were not associated with NSCLC. C1C2 genotype was less frequent whereas both C1C1 and C2C2 homozygotes were more frequent in patients than in controls (χ(2)=7.73; df=2; p=0.021). Patients positive for KIR2DL2 and KIR2DS2 gene and homozygous for the C1 ligand were 6 times more likely to respond to treatment than those with other genotypes (p=0.034). In accordance with this, patients with the KIR2DL2+/KIR2DS2+, C1C1 genotype survived longer than others (p=0.0094). Median survival was 23months for KIR2DL2/2DS2/C1C1-positive patients, but only 10 months for those with other genotypes.

[Beta-blockers usage in cardio-vascular diseases co-existing with COPD]. / Stosowanie beta-blokerów w chorobach sercowo-naczyniowych wspólistniejacych z przewlekla obturacyjna choroba pluc.

Chronic obstructive pulmonary disease (COPD) is one of the most frequent chronic diseases. Slightly reversable and progressive decrease in airflow through the airways is characteristic for the disease. It has been brought up last years that COPD course influences not only pulmonary system status but also many co-existing diseases in the eldery, especially cardio-vascular diseases, such as: ischaemic heart disease, hypertension, heart arrythmias, heart infarction. Wide usage and established position in the treatment of cardio-vascular diseases have the antagonists of beta-adrenergic receptors (beta-blockers). The aim of this work was the combination of the studies results quoted in the literature about the usage of beta-blockers in cardiovascular diseases co-existing with COPD. Conclusions. Nowadays there are no unambiguous recommendations for the usage of beta-blocker in patients with COPD and the decision about including them into treatment depends on the individually estimated risk of complications.

[Application of metabolomic in COPD diagnosing]. / Metody metabolomiczne jako nowe narzedzie diagnostyki przewleklej obturacyjnej choroby pluc.

Chronic obstructive pulmonary disease (COPD) is very heterogeneous, with multiple phenotypes and hardly predictable clinical course. There are no clearly defined biomarkers measuring its progress and advancement. In the recent years, development of modem measurement techniques, first of all the nuclear magnetic resonance and mass spectrometry, allowed their widespread use in biological research. These techniques can analyze tens to several thousands of fine chemicals. Together with chemometric analysis create new diagnostic tool--metabolomics, which evaluates the biochemical processes in biological systems with an assessment of metabolome (the set of all metabolites--small molecules compounds MW < 1000 Da found in the biological material). This in turn makes possible to monitor the quantitative and qualitative changes in activity of the body's metabolism at the cellular level. Theoretically, this may allow to detect disturbances of homeostasis before the onset of clinical symptoms and yet measurable laboratory changes. The results, of the studies so far relatively few, studies with the use of metabolomic methods in COPD suggest that it might be possible to differentiate COPD from other diseases, as well as diagnosing patients with COPD, including disease stratification and severity. It is necessary to conduct further research in order to assess the sensitivity and specificity of these methods in COPD.

[Serum chitotriosidase activity as a biomarker of pulmonary sarcoidosis]. / Aktywnosc chitotriozydazy jako biomarker plucnej postaci sarkoidozy.

Sarcoidosis is a multisystemic granulomatous disorder of unknown etiology, which is characterized by a variable clinical presentation and course. The diagnosis of this disease is usually supported by the three elements: compatible clinical and radiologic findings, tissue biopsy specimen that reveals noncaseating epithelioid granulomas and the absence of known granulomagenic agent. During the last years the new diagnostic methods have been discovered, but serum markers of the sarcoidosis are still under studying. Among the potential markers of sarcoidosis, a recently proposed indicator is chitotriosidase, a chitinase produced by chronically activated macrophages. The review of the literature showed that chitotriosidase activity is only a surrogate biomarker to confirm diagnosis, but is a useful marker for disease activity monitoring and prognosis. The correlation with the radiological stages of disease suggest that determination of chitotriosidase activity could decrease the number of X-ray examination.

Galectin-3 and cyclin D1 expression in non-small cell lung cancer.

INTRODUCTION: Lung cancer is a major cause of mortality and morbidity worldwide. Galectin-3 is multifunctional protein, which is involved in regulation of cell growth, cell adhesion, cell proliferation, angiogenesis and apoptosis. Cyclin D1 together with other cyclin plays an important role in cell cycle control. Cyclin D1 regulates the G1-to-S phase transition. The aim of this study was the evaluation of correlations between clinicopathological findings and cyclin D1 and galectin-3 expression in non-small cell lung cancer (NSCLC). We wanted also to analyze the prognostic value of cyclin D1 and galectin-3 expression. Moreover we tried to evaluate the correlations between galectin-3 and cyclin D1 expression in tumor tissue. MATERIALS AND METHODS: We used the immunochemistry method to investigate the expression of galectin-3 and cyclin D1 in the paraffin-embedded tumor tissue of 47 patients (32 men and 15 women; mean age 59.34 ± 8.90). years. We used monoclonal antibodies to cyclin D1 (NCL-L-cyclin D1-GM clone P2D11F11 NOVO CASTRA) and to galectin-3 (mouse monoclonal antibody NCL-GAL3 NOVO CASTRA). RESULTS: Galectin-3 expression was positive in 18 cases (38.29%) and cyclin D1 in 39 (82.97%). We showed only weak trend, that galectin-3 expression was lower in patients without lymph node involvement (p = 0.07) and cyclin D1 expression was higher in this group (p = 0.080). We didn't reveal differences in cyclin D1 and galectin-3 expression in SCC and adenocarcinoma patients. We didn't demonstrated also differences in galectin-3 and cyclin D1 expression depending on disease stage. Moreover we analyzed the prognostic value of cyclin D1 expression and galectin-3 in all examinated patients and separately in SCC and in adenocarcinoma and in all stages, but we didn't find any statistical differences. We demonstrated that in galectin-3 positive tumors cyclin D1 expression was higher (96.55% vs 61.11%, Chi2 Yatesa 7.53, p = 0.0061) and we revealed negative correlation between cyclin D1 and galectin-3 expression (R Spearman -0.458, p = 0.0011). In squamous cell lung cancer we didn't observed correlations between these both examinated markers (R = -0.158, p = 0.460), and in adenocarcinoma the negative correlation was very strong (R = -0.829 p = 0.000132). CONCLUSIONS: We didn't reveal any important correlations between clinicopathological findings and galectin-3 and cyclin D1 expression and in non small cell lung cancer. We didn't observed also prognostic value of cyclin D1 or galectin-3 expression. But we showed higher cyclin D1 expression in galectin-3 negative tumor tissues. We revealed also differences in correlations between galectin-3 and cyclin D1 expression in two main histopathological types of NSCLC.

Correlation between expression of metallothionein and expression of Ki-67 and MCM-2 proliferation markers in non-small cell lung cancer.

BACKGROUND: Metallothioneins (MTs) are low molecular weight proteins present both in normal and neoplastic cells. They protect cells from the effects of heavy metals and from damage induced by free radicals. MT bind heavy metals, exert an anti-apoptotic effect and stimulate proliferation of neoplastic cells. The role of MTs in carcinogenesis has not been fully clarified yet. This study aimed at the evaluation of the intensity of metallothionein (MT-I/II) expression in various histological types of non-small cell lung cancer (NSCLC) and correlation of the expression intensity with clinical/pathological parameters and Ki-67 and minichromosome maintaince protein 2 (MCM-2) proliferation markers. PATIENTS AND METHODS: The studies were performed on archival material, originating from 145 patients, 105 men and 40 women (65 adenocarcinomas, 67 squamous cell carcinomas, 13 large cell carcinomas). RESULTS: A positive correlation was noted between expression of MT-I/II and expressions of Ki-67 (r=0.1863, p=0.0248) and MCM-2 (r=0.1766, p=0.0336) in NSCLC overall. The most pronounced expression of MT-I/II was noted in the large cell carcinomas. The expression of MT-I/II was significantly lower in the adenocarcinomas than in the squamous cell carcinomas (p=0.0028) and large cell carcinomas (p=0.0485). The expression of MT-I/II showed no differences related to individual degrees of NSCLC malignancy. Univariate analysis demonstrated no significant differences in overall survival related to the expression intensity of MT-I/II, Ki-67 or MCM-2, but the survival of the patients with high expression of MT-I/II and Ki-67 in the neoplastic cells, as compared to low expression of MT-I/II and Ki-67, was shorter (the difference approached statistical significance, p=0.067). CONCLUSION: MT-I/II expression is evident in proliferating NSCLC neoplastic cells, pointing to the prognostic importance of parallel expression of MT-I/II and Ki-67.

CTLA-4, CD28, and ICOS gene polymorphism associations with non-small-cell lung cancer.

Polymorphisms in genes encoding CD28, ICOS, and CTLA-4 were demonstrated to be associated with susceptibility to malignancies. To the best of our knowledge, no study on this association has been performed in a Caucasian population for non-small-cell lung cancer (NSCLC). In the present work, we investigated the polymorphisms CTLA-4c.49A>G (rs231775), CTLA-4g.319C>T (rs5742909), CTLA-4g.*642AT(8_33), CTLA-4g.*6230G>A (CT60) (rs3087243), CTLA-4g.*10223G>T (Jo31) (rs11571302), CD28c.17+3T>C (rs3116496), and ICOSc.1554+4GT(8_15) in 208 NSCLC patients and 326 controls. The distributions of the allele and genotype were similar in both groups for CTLA-4, CD28, and ICOS gene polymorphisms. However, we noted a tendency toward overrepresentation of individuals possessing the CTLA-4c.49A>G[A] allele in NSCLC patients compared with controls (0.84 vs 0.79, p = 0.09). The association became significant compared with controls in women for the CTLA-4c.49A>G[A] allele and CTLA-4c.49A>G[AA] genotype (0.67 vs 0.54, p = 0.01, and 0.47 vs 0.30, p = 0.02; respectively). Moreover, the constellation of alleles CTLA-4c.49A>G[A]/CT60[G]/CD28c.17+3T>C[T]/ICOSc.1554+4GT(8_15)[>10] increased the risk of NSCLC about 2-fold (p = 0.002). The same constellation of alleles combined with smoking, CTLA-4g.319C>T[T], and ICOSc.1554+4GT(8_15)[>10] was associated with a decreased overall survival rate. In conclusion, the constellation of specific alleles in CTLA-4, CD28, and ICOS genes contributes to the susceptibility and clinical course of NSCLC.