ABSTRACT
This study aims to assess early effects of chemotherapy on symptom alleviation, nutritional status, and mental health in elderly patients with advanced non-small-cell lung cancer (NSCLC). This prospective study included 45 NSCLC patients (32 males, 13 females) aged 65-82 years (mean age 70.0 ± 4.5 years) with good performance status. Assessments were conducted immediately after diagnosis and after two chemotherapy cycles, focusing on nutritional status (assessed with MNA questionnaire), quality of life (QoL, based on FACT-L and FACT-TOI questionnaires), lung cancer-related symptoms (based on LCSS), and mental health (based on PHQ-9 questionnaire). Despite significant alleviation of symptoms like cough, dyspnea, and body weight loss, there was no significant correlation between changes in symptoms burden and changes in nutritional status (r2 = 0.122, P = 0.427), and change of patients' mental condition (r2 = -0.141, P = 0.255). No significant QoL changes were noted, but a decrease in severe depression frequency was observed. The improvement of patients' mental condition was related strictly to the improvement of nutritional status (r2 = -0.589, P < 0.001). The study highlights the vital link between nutritional status and mental health in elderly NSCLC patients, emphasizing the need for integrated care approaches that address both aspects to enhance treatment effectiveness and patient well-being.
ABSTRACT
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.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/genetics , Down-Regulation , Lung Neoplasms/genetics , Antigen Presentation , Peptides/genetics , Aminopeptidases/genetics , Minor Histocompatibility Antigens/geneticsABSTRACT
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.
Subject(s)
Adenocarcinoma of Lung , Adenocarcinoma , Carcinoma, Non-Small-Cell Lung , Carcinoma, Squamous Cell , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Programmed Cell Death 1 Receptor/genetics , B7-H1 Antigen/genetics , Genetic Predisposition to Disease , Adenocarcinoma/genetics , Carcinoma, Squamous Cell/genetics , Polymorphism, Single Nucleotide , Prognosis , Hepatitis A Virus Cellular Receptor 2/geneticsABSTRACT
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.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Kidney Neoplasms , Lung Neoplasms , Female , Humans , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Smokers , T-Lymphocytes/pathology , Polymorphism, Single Nucleotide , Receptors, Immunologic/geneticsABSTRACT
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.
ABSTRACT
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.
Subject(s)
Antigen Presentation/genetics , Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/etiology , Lung Neoplasms/genetics , Polymorphism, Genetic , Adult , Aged , Alleles , Aminopeptidases/genetics , Carcinoma, Non-Small-Cell Lung/diagnosis , Female , Genetic Association Studies , Genetic Predisposition to Disease , Genotype , Haplotypes , Humans , Lung Neoplasms/diagnosis , Male , Middle Aged , Minor Histocompatibility Antigens/genetics , Neoplasm Staging , Polymorphism, Single Nucleotide , Risk Assessment , SmokersABSTRACT
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.
Subject(s)
Copper/blood , Lung Neoplasms/blood , Lung Neoplasms/mortality , Zinc/blood , Aged , Anthropometry , Cohort Studies , Female , Humans , Kaplan-Meier Estimate , Lung Neoplasms/therapy , Male , Middle Aged , Neoplasm Staging , Nutritional Status , Prognosis , Prospective Studies , Serum/chemistryABSTRACT
In lung cancer (LC), alterations in redox balance are extensively observed and are a consequence of disease as well as co-occurrent with smoking. We previously demonstrated that metabolic disturbances such as trace element status and carbohydrate metabolism alterations are linked with redox status. The aim of this study was to evaluate relationships between the serum parameters of lipid metabolism and redox balance in LC patients. Serum parameters of lipid metabolism, i.e. total cholesterol (T-C), HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), triglycerides (TG), T-C:HDL-C ratio, non-HDL-C, apolipoprotein A1 (Apo-A1), apolipoprotein B (Apo-B) and Apo-B:Apo-A1 ratio, as well as systemic redox status, i.e. total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), vitamin E (VE), vitamin C (VC), malonyldialdehyde (MDA), conjugated dienes (CD), and 4-hydroxynonenal (4-HNE) were determined in 92 LC patients and 82 control subjects (CS). LC women had significantly lower T-C and LDL-C, and higher TG, while HDL-C, Apo-A1 and Apo-B were significantly decreased in LC patients regardless of sex, when compared to CS. LC men had alterations in the systemic total redox balance such as lower TAS and higher OSI than CS men. LC women had lower VC, but VE was decreased in LC patients, regardless of sex. We observed higher lipid peroxidation in LC patients expressed via higher 4-HNE and CD. Systemic redox disturbances were associated with serum lipid alterations: TOS and OSI were positively correlated with T-C:HDL-C ratio and Apo-B:Apo-A1 ratio and negatively with HDL-C. The parameters of lipid peroxidation CD and MDA were significantly associated with variables reflecting lipid disturbances. The observed correlations were strengthened by general overweight/obesity, abdominal obesity, hypertriglyceridemia and non-smoking status. In conclusion, parameters related to lipid alterations are associated with oxidative stress in LC patients. The largest contribution from lipid parameters was revealed for T-C:HDL-C ratio, HDL-C and Apo-B:Apo-A1 ratio, while the largest contribution from redox status was revealed for OSI and VE. Overweight, obesity, hypertriglyceridemia and non-smoking status intensified these relationships.
Subject(s)
Lipid Metabolism , Lung Neoplasms/blood , Oxidative Stress , Aged , Apolipoprotein A-I/blood , Apolipoprotein B-100/blood , Biomarkers/blood , Case-Control Studies , Cholesterol/blood , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Female , Humans , Male , Middle Aged , Oxidation-Reduction , Triglycerides/bloodABSTRACT
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.
Subject(s)
Glycemic Index , Glycemic Load , Lung Neoplasms , Nutritional Status , Antioxidants/physiology , Case-Control Studies , Diet , Female , Humans , Lung Neoplasms/physiopathology , Male , OxidantsABSTRACT
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. ß-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.
Subject(s)
Glucose/metabolism , Lung Neoplasms/metabolism , Adult , Aged , Aged, 80 and over , Case-Control Studies , Female , Humans , Male , Middle Aged , Models, Biological , Nutritional Status , Oxidation-ReductionABSTRACT
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.
Subject(s)
Copper/blood , Lung Neoplasms/blood , Manganese/blood , Zinc/blood , Antioxidants/metabolism , Bilirubin/blood , Humans , Oxidation-Reduction , Oxidative Stress/physiology , Serum Albumin, Human/metabolism , Trace Elements/blood , Uric Acid/bloodABSTRACT
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.
Subject(s)
Selectins/blood , Sleep Apnea Syndromes/blood , Sleep Apnea, Obstructive/blood , Biomarkers/blood , C-Reactive Protein/metabolism , Cardiovascular Diseases/blood , Cardiovascular Diseases/metabolism , Cholesterol, HDL/blood , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Male , Middle Aged , Polysomnography/methods , Risk Factors , Sleep Apnea Syndromes/metabolism , Sleep Apnea, Obstructive/metabolismABSTRACT
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.
Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , Molecular Targeted Therapy , Mutation , Carcinoma, Non-Small-Cell Lung/drug therapy , Humans , Lung Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic useABSTRACT
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.
Subject(s)
Disorders of Excessive Somnolence/etiology , Hypertension/epidemiology , Sleep Apnea, Obstructive/epidemiology , Sleep Stages , Adult , Age Factors , Aged , Body Mass Index , Comorbidity , Female , Humans , Male , Middle Aged , Polysomnography , Risk FactorsABSTRACT
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.
Subject(s)
Anemia/diagnosis , Lung Neoplasms/complications , Malnutrition/diagnosis , Aged , Aged, 80 and over , Anemia/epidemiology , Humans , Iron/blood , Male , Middle Aged , Nutritional Status , Predictive Value of Tests , PrevalenceABSTRACT
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.
ABSTRACT
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.
Subject(s)
Apoptosis , Biomarkers/blood , Fas Ligand Protein/blood , Proto-Oncogene Proteins c-bcl-2/blood , Pulmonary Disease, Chronic Obstructive/diagnosis , Tumor Necrosis Factor-alpha/blood , Tumor Suppressor Protein p53/blood , Adult , Aged , Enzyme-Linked Immunosorbent Assay , Female , Humans , Middle Aged , Pulmonary Disease, Chronic Obstructive/blood , Pulmonary Disease, Chronic Obstructive/physiopathology , Severity of Illness IndexABSTRACT
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.
Subject(s)
Aminopeptidases/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , Minor Histocompatibility Antigens/genetics , Polymorphism, Single Nucleotide , Adult , Aged , Asian People , Carcinoma, Non-Small-Cell Lung/metabolism , China , Female , Gene Expression Regulation, Neoplastic , Genetic Predisposition to Disease , Genotype , HLA Antigens/metabolism , Haplotypes , Humans , Lung Neoplasms/metabolism , Male , Middle Aged , Poland , Risk , White PeopleABSTRACT
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.
ABSTRACT
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.