ABSTRACT
BACKGROUND: Considering that the innate immune system plays a pivotal role in the pathogenesis of chronic obstructive pulmonary disease (COPD), we hypothesized that functional single-nucleotide polymorphisms (SNPs) of innate immune genes affect the disease phenotype and prognosis. AIM: To elucidate the contribution of common functional TLR2 and TLR4 SNPs and genotypic deficiency of the mannose-binding lectin (MBL) protein, both as single parameters and in combination, in Greek COPD patients. RESULTS: In a cohort of 114 Greek COPD patients, we confirmed that the presence of TLR4-D299G or TLR4-T399I SNPs was significantly associated with an earlier COPD stage (p = 0.003 and p = 0.009, respectively). In comparison, the absence of any analyzed polymorphism, including those of TLR2-R753Q and genotypic MBL deficiency, was significantly associated with a more severe disease phenotype, characterized by more frequent exacerbations (p = 0.045). CONCLUSION: Our findings support the notion that the presence of innate immune SNPs, such as functional polymorphisms of TLRs along with MBL deficiency, might exert a protective effect on the COPD phenotype, similar with other immune-mediated disorders.
Subject(s)
Genotype , Phenotype , Polymorphism, Genetic/genetics , Pulmonary Disease, Chronic Obstructive/genetics , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Immunity, Innate/genetics , Male , Mannose-Binding Lectin/deficiency , Mannose-Binding Lectin/genetics , Mannose-Binding Lectin/immunology , Metabolism, Inborn Errors/diagnosis , Metabolism, Inborn Errors/genetics , Metabolism, Inborn Errors/immunology , Polymorphism, Single Nucleotide/genetics , Prognosis , Protective Factors , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/immunology , Risk Factors , Smoking/adverse effects , Smoking CessationABSTRACT
Mesothelioma is a malignancy with poor prognosis, with an average 5-year survival rate being less than 9%. This type of cancer is almost exclusively caused by exposure to asbestos. A long exposure can cause mesothelioma and so can short ones, as each exposure is cumulative. We report a case of a 26-year-old male who was exposed to asbestos during his primary school years from the age of 6 to 12. Although the tumor mainly affects older men who in their youth were occupationally exposed to asbestos, malignant mesothelioma can also occur in young adults. A medical history was carefully taken and asbestos exposure was immediately mentioned by the patient. We conducted biopsy on the right supraclavicular lymph node. The patient was not a candidate for surgery, and chemotherapy treatment was initiated. While patient's chemotherapy is still ongoing, no other similar cases of students or teachers have been traced up to date from his school. The school building was demolished in January 2009.
ABSTRACT
Vascular endothelial growth factor (VEGF) is known to play crucial role in tumour angiogenesis. It is demonstrated that VEGF can be up-regulated by oxidative stress. The aim of this study was to determine the serum VEGF levels and oxidative stress in patients with primary lung cancer and to investigate their association with clinicopathologic factors. We measured serum VEGF levels and oxidative stress in 63 patients (age 63.02+/-1.12 S.E.M.) with primary lung cancer before any treatment (39 NSCLC and 24 SCLC; 6 patients stage I, 3 stage II, 25 stage III and 29 stage IV) and 25 normal subjects. The serum VEGF levels were measured with enzyme linked immunosorbent assay. Serum oxidative stress levels were detected by a commercially available assay (D-ROMs test, Diacron, Grossetto, Italy). The levels of oxidative stress in patients were higher than those in normal subjects (555.3+/-30.35 UCarr vs. 360.1+/-17.46 UCarr). Additionally, a significant difference was found in serum VEGF levels between lung cancer patients and healthy control subjects (428.1+/-38.42pg/ml vs. 298.8+/-19.89pg/ml, respectively, p=0.040). Interestingly, serum oxidative stress presented a significant correlation with serum VEGF levels in patients with lung cancer (r=0.542, p=0.002). Serum VEGF levels were significantly associated with the clinical staging (N-stage) of the patients (p=0.023), performance status (p=0.004) and age (p=0.004). In conclusion, oxidative stress and VEGF are significantly increased in patients with primary lung cancer. The correlation between them might implicate new aspects of the mechanisms controlling tumour angiogenesis and may present clinical interest in the future. Further studies are warranted to evaluate the role of oxidative stress and VEGF as possible biomarkers for the diagnosis and follow-up of patients with lung cancer.
