Down-regulation of ERAP1 mRNA expression in non-small cell lung cancer.

BACKGROUND: ERAP1 is a major aminopeptidase that serves as an editor of the peptide repertoire by trimming N-terminal residues of antigenic peptides, creating a pool of peptides with the optimal length for MHC-I binding. As an important component of the antigen processing and presenting machinery - APM, ERAP1 is frequently down-regulated in many cancers. Since ERAP1 expression has not yet been thoroughly investigated in non-small cell lung cancer (NSCLC), we decided to analyze ERAP1 mRNA levels in tissues collected from NSCLC patients. METHODS: Using real-time qPCR, we evaluated ERAP1 mRNA expression in samples of tumor and adjacent non-tumor tissue (serving as control tissue) from 61 NSCLC patients. RESULTS: We observed a significantly lower level of ERAP1 mRNA expression in tumor tissue (MedTumor = 0.75) in comparison to non-tumor tissue (MedNon-tumor = 1.1), p = 0.008. One of the five tested polymorphisms, namely rs26653, turned out to be significantly associated with ERAP1 expression in non-tumor tissue (difference [d] = 0.59 CI95% (0.14;1.05), p = 0.0086), but not in tumor tissue. The levels of ERAP1 mRNA expression did not affect the overall survival of NSCLC patients, either in the case of the tumor (p = 0.788) or in non-tumor (p = 0.298) tissue. We did not detect any association between mRNA ERAP1 expression level in normal tissue and: (i) age at diagnosis (p = 0.8386), (ii) patient's sex (p = 0.3616), (iii) histological type of cancer (p = 0.7580) and (iv) clinical stage of NSCLC (p = 0.7549). Furthermore, in the case of tumor tissue none of the abovementioned clinical parameters were associated with ERAP1 expression (p = 0.76). CONCLUSION: Down-regulation of ERAP1 mRNA observed in NSCLC tissue may be related to tumor immune evasion strategy. The rs26653 polymorphism can be considered an expression quantitative trait locus (eQTL) associated with ERAP1 expression in normal lung tissue.

Non-small cell lung cancer - mutations, targeted and combination therapy.

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.

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.

Total antioxidant status in lung cancer is associated with levels of endogenous antioxidants and disease stage rather than lifestyle factors - preliminary study.

AIM OF THE STUDY: Decreased total antioxidant capacity (TAC) has been reported in different neoplasms, including lung cancer. However, no study concerning the relationship between endogenous antioxidants, lifestyle factors, and TAC has been conducted among lung cancer patients. The purpose of the study was to investigate the associations between endogenous antioxidants, severity of disease, lifestyle factors, and TAC in lung cancer patients. MATERIAL AND METHODS: The study was conducted among 59 lung cancer patients. The levels of total antioxidant status (ATBS method), endogenous antioxidants, and C-reactive protein were measured in patients' sera automatically. Dietary habits of the subjects were evaluated based on the Food Frequency Questionnaire (FFQ) on the day of admission to hospital. RESULTS: We found a positive correlation between serum albumin, uric acid (UA), and TAC and a negative correlation between CRP and TAC. Moreover, TAC was significantly positively associated with disease stage. We did not find any significant relationship between the frequency of selected food consumption and TAC in lung cancer patients, except for a positive correlation between the frequency of refined cereal products consumption and TAC level. Smoking status did not correlate with TAC. CONCLUSIONS: Total antioxidant status of lung cancer patients results from their disease stage and levels of endogenous antioxidants rather than from lifestyle factors. The lack of influence of diet and smoking on the TAC presumably result from disturbed homeostasis in which cancer, while developing, could determine the redox state to a greater extent than lifestyle factors.

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.

Identification of soluble supramolecular FN-fibrin complexes in human plasma.

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.

[Smoking among patients with obstructive sleep apnea syndrome--preliminary report]. / Palenie tytoniu u pacjentów z zespolem obturacyjnego bezdechu sródsennego--doniesienie wstepne.

UNLABELLED: Association of smoking with the occurrence and severity of the obstructive sleep apnea syndrome (OSAS) is poorly understood. THE AIM OF THE STUDY: The evaluation of smoking habits among the patients hospitalized with the suspicion and diagnosis of the OSAS. The possible relationship between smoking and severity of OSAS and the occurrence of concomitant diseases occurrence was also evaluated. MATERIAL AND METHODS: 82 patients has been included into the study: 11 without OSAS (apnea/hypopnea index-AHI < 5/hour) and 71 with OSAS of varying severity (AHI 7-74/hours). RESULTS: Forty six patients with OSAS were smokers or ex-smokers, and 5 persons from a group without OSAS were ex-smokers. Patients with OSAS who smoked at least 20 pack years had significant higher AHI (54.5/h) than non-smokers (38.5/h) and patients smoking less than 20 pack years (35.9/h). These groups of patients did not differ according to BMI (36.8 kg/m2, 38.8 kg/m2, 36.3 kg/ms). Smokers with OSAS more frequently had concomitant cardiovascular diseases than non-smokers with OSAS (86.1% and 23.1% respectively). CONCLUSION: Smoking influences the severity of OSAS independently of the degree of obesity.

Common inherited variants of PDCD1, CD274 and HAVCR2 genes differentially modulate the risk and prognosis of adenocarcinoma and squamous cell carcinoma.

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.

Lung cancer in patients under the age of 40 years.

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 diagnosis, character of changes visible in radiological imaging, time that passed from the first symptoms to reporting to a doctor and to establishing a diagnosis, type of diagnostic method used in establishing the final diagnosis, histopathologic type of cancer, degree of cancer progression. RESULTS: The results have been compared with a peer group who had been diagnosed 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 earlier group in which 57% of patients had small cell lung cancer (57%). The incidence is equally distributed between both sexes, although there is an evident increase in female lung cancer cases. In the majority of patients the clinical presentation 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 bronchoscopy acquired specimen. Time course from symptoms to diagnosis tends to be shorter than 20 years ago.

The association of BTLA gene polymorphisms with non-small lung cancer risk in smokers and never-smokers.

Introduction: Lung cancer is the predominant cause of death among cancer patients and non-small cell lung cancer (NSCLC) is the most common type. Cigarette smoking is the prevailing risk factor for NSCLC, nevertheless, this cancer is also diagnosed in never-smokers. B and T lymphocyte attenuator (BTLA) belongs to immunological checkpoints which are key regulatory molecules of the immune response. A growing body of evidence highlights the important role of BTLA in cancer. In our previous studies, we showed a significant association between BTLA gene variants and susceptibility to chronic lymphoblastic leukemia and renal cell carcinoma in the Polish population. The present study aimed to analyze the impact of BTLA polymorphic variants on the susceptibility to NSCLC and NSCLC patients' overall survival (OS). Methods: Using TaqMan probes we genotyped seven BTLA single-nucleotide polymorphisms (SNPs): rs2705511, rs1982809, rs9288952, rs9288953, rs1844089, rs11921669 and rs2633582 with the use of ViiA 7 Real-Time PCR System. Results: We found that rs1982809 within BTLA is associated with NSCLC risk, where carriers of rs1982809G allele (AG+GG genotypes) were more frequent in patients compared to controls. In subgroup analyses, we also noticed that rs1982809G carriers are significantly overrepresented in never-smokers, but not in smokers compared to controls. Additionally, the global distribution of the haplotypes differed between the never-smokers and smokers, where haplotypes A G G C A, C G A C G, and C G A T G were more frequent in never-smoking patients. Furthermore, the presence rs1982809G (AG+GG genotypes) allele as well as the presence of rs9288953T allele (CT+TT genotypes) increased NSCLC risk in females' patients. After stratification by histological type, we noticed that rs1982809G and rs2705511C carriers were more frequent among adenocarcinoma patients. Moreover, rs1982809G and rs2705511C correlated with the more advanced stages of NSCLC (stage II and III), but not with stage IV. Furthermore, we showed that rs2705511 and rs1982809 significantly modified OS, while rs9288952 tend to be associated with patients' survival. Conclusion: Our results indicate that BTLA polymorphic variants may be considered low penetrating risk factors for NSCLC especially in never-smokers, and in females, and are associated with OS of NSCLC patients.

[The cyclin A, B1, D1 and E expression in advanced non-small cell lung cancer--stages IIIB-IV (preliminary report)]. / Ekspresja cyklin A, B1, D1 i E w zaawansowanym niedrobnokomórkowym raku pluca--stadia IIIB-IV (doniesienie wstepne).

UNLABELLED: Lung cancer is the leading cause of cancer death in the majority of developed countries. Uncontrolled cell proliferation is the hallmark of malignant tumours. Cyclins play an important role in cell cycle regulation. The aim of this study was to evaluate the expression of cyclins A, B1, D1 and E in advanced non-small cell lung cancer (stages IIIB-IV) with its prognostic significance. MATERIAL AND METHOD: An immunohistochemical assessment of cyclins A, B1, D1 and E expression was performed in the paraffin-embedded tumor tissues of 19 patients (9 men and 10 women). The mean was age 59 +/- 6.64 years. 9 patients were in IIIB and 10 in IV. The 2-years survival rate was evaluated. RESULTS: We showed positive cyclin A expression in 13 tumor tissue specimens (68%), cyclin B1 in 3 (16%), cyclin D1 in 9 (47%) and cyclin E in 7 (37%). We analyzed the prognostic value of examinated cyclins in all NSCLC patients and separately in patients with squamous cell lung cancer and adenocarcinoma and in patients in stage IIIB and IV, but we have no found any correlations. We did not find also any differences in examinated cyclins expression depending on stages nor different histopathological types. CONCLUSION: We did not observe prognostic value of cyclins A, B1, D1 or E expression in advanced non-small cell lung cancer.

[Coexistence of obstructive sleep apnea syndrome and chronic obstructive pulmonary disease]. / Wspólistnienie zespolu obturacyjnego bezdechu sródsennego i przewleklej obturacyjnej choroby pluc.

INTRODUCTION: 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. MATERIAL AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

[Assessment of sociodemographic and nutritional status of lung cancer patients]. / Ocena statusu socjodemograficznego i stanu odzywienia chorych z rakiem pluca.

Low sociodemographic status positively correlates with the risk of lung cancer. Nutritional status assessed during diagnosis of cancer may be a useful predictive factor for response to therapy and influences the quality of life and life expectancy after oncological therapy. The aim of this study was to assess the sociodemographic and nutritional status of patients. Lower Silesian Centre of Lung Diseases, diagnosed with lung cancer. 81 cases and 125 subjects formed the control group were included in this study. The questionnaire about sociodemographic status was performed among all respondents as well as MNA questionnaire and anthropometric measurements for evaluating nutritional status. Lower level of education, lower employment status and more frequent tobacco addiction was found in patient group then in control individuals. Nutritional status of patients was worse than the control group, which has been demonstrated mainly through a MNA questionnaire and arm circumference measurements. The risk of malnutrition or diagnosed malnutrition found in most patients assessed by MNA test may increase the likelihood of complications during treatment.

Serum Total SOD Activity and SOD1/2 Concentrations in Predicting All-Cause Mortality in Lung Cancer Patients.

Redox status disturbances are known during carcinogenesis and may have influence on patients' survival. However, the prediction of mortality in lung cancer patients based on serum total SOD activity, and concentrations of its isoforms, has not been studied to date. This prospective cohort study has following aims: (1) to evaluate the disturbances in serum SOD activity and SOD1/2 concentrations; (2) to assess the implications of these alterations with regard to biochemical variables and clinical data, and (3) to investigate the association between serum SOD activity, SOD1/2 concentrations, and all-cause mortality in lung cancer patients. Serum total SOD activity and SOD1, SOD2, albumin, CRP, and ceruloplasmin concentrations were determined in lung cancer patients (n = 190) and control subjects (n = 52). Additionally, patients were characterized in terms of biochemical, clinical, and sociodemographic data. Multiple Cox regression models were used to estimate the association between all-cause death and SOD-related parameters. All-cause mortality in lung cancer was positively associated with serum SOD1 and SOD2 concentrations. Clinical stage III and IV disease was the strongest predictor. The utility of the evaluated parameters in predicting overall survival was demonstrated only for SOD1. Serum SOD1 and SOD2 concentrations were shown to positively affect all-cause mortality in lung cancer patients, but SOD1 seems to be a better predictor than SOD2.

Polymorphisms of Antigen-Presenting Machinery Genes in Non-Small Cell Lung Cancer: Different Impact on Disease Risk and Clinical Parameters in Smokers and Never-Smokers.

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.

[Dietetic aspects of giving up smoking]. / Zalecenia dietetyczne dla osób rezygnujacych z palenia tytoniu.

Smoking cessation should be connected with multidirectional life style change. Proper diet can be helpful for enhancing the efficacy of this process. Authors discuss selected aspects of diet modification for smoking quitters. The diet aspects of preventing weight gain, coexisting cardiovascular diseases and detoxication were discussed.

[Nutritional knowlegde and lifestyle of obese patients with diagnosed obturative sleep apnea]. / Wiedza zywieniowa oraz wybrane elementy stylu zycia otylych osób z rozpoznanym obturacyjnym bezdechem w czasie snu.

The study was aimed, therefore, at evaluating the nutritional knowledge and selected elements of lifestyle of obese patients with diagnosed obstructive sleep apnea (OSA), treated at the Lower Silesia Center of Pulmonary Diseases in Wroclaw. Assessment of nutritional knowledge was conducted among 49 patients including 12 women and 37 men with diagnosed obstructive sleep apnea (OSA), treated at the Lower Silesia Center of Pulmonary Diseases in Wroclaw. The nutritional knowledge and selected elements of lifestyle were evaluated by means of own-construct, standardized questionnaire elaborated at the Chair of Human Nutrition, Wroclaw University of Life and Environmental Sciences. It included questions from different fields referring to, among others: knowledge on rational nutrition, type of physical activity, frequency of cigarette smoking, etc. Despite the demonstrated some knowledge of good nutrition, its use by patients with OSA in everyday life raises many objections. This could possibly result from the message is not binding on the correct nutrition to their own health. Found in the studied group of patients with OSA obesity and low physical activity, evidence of the need to integrate into the process of treatment of individual dietary counseling.

Serum and Whole Blood Cu and Zn Status in Predicting Mortality in Lung Cancer Patients.

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. Naïve-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.

Cyclin A and Cyclin E expression in resected non-small cell lung cancer stage I-IIIA.

BACKGROUND: Lung cancer is the leading cause of cancer death in the majority of developed countries. Cyclin E regulates the the G(1)-S phase transition of the cell cycle. Cyclin A increases during the S- and G(2)-phases, and is a regulator of the transition to mitosis.The aim of this study was to evaluate the prognostic significance of cyclin A and cyclin E expression in primary, resected stage I-IIIA non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The expression of cyclin A and E was investigated in the paraffin-embedded tumor tissue of 71 patients (53 men and 18 women; age 59.27+/-8.50 years), using a monoclonal antibodies to cyclin A and to cyclin E. RESULTS: Forty-seven out of 71 (66%) tumor tissue specimens were positive for cyclin A and twenty-six (37%) were positive for cyclin E. In the majority of cases, nuclear staining was apparent. Cyclin A and cyclin E expression was significantly higher in squamous cell carcinoma than in adenocarcinoma (cyclin A: Chi(2) Yates'a 4.6; p=0.032; cyclin E: Chi(2) Yates'a 5.12: p=0.023). The prognostic value of cyclin A and E expression was examinated in all patients and in patients with squamous cell lung cancer and adenocarcinoma and separately for every stage, but no correlations were found. CONCLUSION: No prognostic value of cyclin A and E expression was found in NSCLC, but significantly higher cyclin A and E expression was found in squamous cell carcinomas than in adenocarcinomas.

[Expression of p53, bcl-2 and nm23 proteins in squamous cell lung cancer]. / Ekspresja bialek p53, bcl-2 i nm23 w plaskonablonkowym raku pluca.

INTRODUCTION: The evaluation of lung cancer molecular profiles is an essential element of the therapeutic process in that type of neoplasm. The analysis of apoptotic and metastasis-linked proteins is an important goal because of the key role of those processes in carcinogenesis. The aim of this study was to evaluate the expression of apoptosis regulatory proteins p53 and bcl-2 as well as antimetastatic marker nm23 in squamous cell lung cancer, taking into account the clinical and pathological data. MATERIAL AND METHODS: Thirty tissue specimens from patients undergoing therapeutic or diagnostic thoracic surgery were included in the study. All markers were assessed with immunohistochemistry method on paraffin-embedded tissue. RESULTS: Nm23 expression was observed less frequently in specimens with cancer cell emboli in blood vessels or lymph node metastasis. In cancers with lymph node metastasis, the coexpression of p53 and bcl-2 was found statistically more often than in lymph node negative cases. There was no correlation between p53, bcl-2 and nm23 expression and 2-years survival time. CONCLUSIONS: Our study indicates a marked heterogeneity of p53, bcl-2 and nm23 expression in squamous cell lung cancer and the potentially unfavorable influence of p53 and bcl-2 coexpression. Less frequent nm23 expression seems to be connected with morphological signs of metastatic process.