hOGG1, p53 genes, and smoking interactions are associated with the development of lung cancer.

This study aimed to investigate the effects of Ser/Cys polymorphism in hOGG1 gene, Arg/Pro polymorphism in p53 gene, smoking and their interactions on the development of lung cancer. Ser/Cys polymorphism in hOGG1 and Arg/Pro polymorphism in p53 among 124 patients with lung cancer and 128 normal people were detected using PCR-RFLP. At the same time, smoking status was investigated between the two groups. Logistic regression was used to estimate the effects of Ser/Cys polymorphism and Arg/Pro polymorphisms, smoking and their interactions on the development of lung cancer. ORs (95% CI) of smoking, hOGG1 Cys/Cys and p53 Pro/ Pro genotypes were 2.34 (1.41-3.88), 2.12 (1.03-4.39), and 2.12 (1.15-3.94), respectively. The interaction model of smoking and Cys/Cys was super-multiplicative or multiplicative, and the OR (95% CI) for their interaction item was 1.67 (0.36 -7.78). The interaction model of smoking and Pro/Pro was super-multiplicative with an OR (95%CI) of their interaction item of 5.03 (1.26-20.1). The interaction model of Pro/Pro and Cys/Cys was multiplicative and the OR (95%CI) of their interaction item was 0.99 (0.19-5.28). Smoking, hOGG1 Cys/Cys, p53 Pro/Pro and their interactions may be the important factors leading to the development of lung cancer.

[Regulating action of iron regulatory protein-2 in iron metabolism of lung cancer].

OBJECTIVE: To discuss the regulating mechanism of iron regulatory protein-2 (IRP2) in the iron metabolism of lung cancer. METHODS: The cultured A549 cells were divided into 3 groups: liposome group (including liposomes 20 mg/L), random oligonucleotide group (SCODN group) and antisense oligonucleotide group (ASODN group). And the liposome-mediated transfection was employed with the liposome and SCODN groups as controls. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to examine the mRNA and protein expressions of iron metabolism-related transferring (Tf), transferrin receptor (TfR) and ferritin (Fn) genes, etc. RESULTS: After a 48-hour transfection, the mRNA expression of Tf had no statistically significant difference among three groups (F = 2.18, P = 0.078); the mRNA expression of TfR in the ASODN group was significantly lower than that in the liposome and SCODN groups (P < 0.05). The expression of Fn mRNA in the ASODN group (0.56 ± 0.06) was higher than that in the liposome (0.36 ± 0.05) and SCODN groups (0.39 ± 0.03) (P < 0.05). After a 48-hour transfection, the IRP2 protein expression of the ASODN group was significantly lower than those of the liposome and SCODN groups (P < 0.05). The Tf protein expression was not statistically different in three groups (F = 2.67, P = 0.088). The TfR protein expression of the ASODN group was lower than those of the liposome and SCODN groups (P < 0.05). And the Fn protein expression of the ASODN group was higher than those of the liposome and SCODN groups (P < 0.05). CONCLUSION: IRP2 may affect the expressions of TfR and Fn in lung adenocarcinoma A549 cells by changing the amount of protein and regulating the iron metabolism.

[Changes of HMGB1 and RAGE in induced sputum from patients with bronchial asthma].

OBJECTIVE: To explore the relationship between HMGB1 (high mobility group box-1) protein and receptor for advanced glycosylation end products (RAGE) and the nosogenesis and severity of bronchial asthma. METHODS: Based on the criteria, the asthma group included 64 acute-onset asthma patients while the control group had 20 healthy cases. The asthma group received a 4-week combination inhalation therapy of budesonide and formoterol. Lung functions and induced sputum examinations were conducted before and after treatment. The percentage of a second forced expiratory volume in the predicted value (FEV(1)%) was recorded. A differential count of neutrophilic leukocyte in reduced sputum was performed. And the sputum levels of HMGB1 and RAGE were detected by ELISA (enzyme linked immunosorbent assay). RESULTS: Prior to treatment, the neutrophilic leukocyte percentage and the levels of HMGB1 and RAGE were all higher than those of control group (P < 0.01). The induced sputum of severe asthma patients had higher levels of neutrophilic leukocyte percentage and HMGB1 than those of mild cases (P < 0.01). But the level of RAGE showed no statistical significance among mild, moderate or severe asthma cases (P > 0.05). The post-treatment levels of neutrophilic leukocyte percentage, HMGB1 and RAGE were lower as compared with the pre-treatment ones (P < 0.01). These three parameters in uncontrolled cases were higher than those in completely controlled cases (P < 0.05); in asthma group, both HMGB1 and RAGE had a negative correlation with FEV(1)% (r = -0.830, r = -0.632, P < 0.01); in induced sputum, both HMGB1 and RAGE had a positive correlation with FEV(1)% (r = 0.820, r = 0.623, P < 0.01). The levels of HMGB1 and RAGE were positively correlated (r = 0.929, P < 0.01). CONCLUSION: Both HMGB1 and RAGE participate in the inflammatory process of asthmatic airway. HMGB1 is correlated with the severity of asthma. And the levels of HMGB1 and RAGE in induced sputum may be employed as reference indices for the observation of therapeutic effects.

[Levels of HMGB1 in induced sputum from patients with asthma and chronic obstructive pulmonary disease].

OBJECTIVE: To explore the relationship between the sputum levels of high mobility group protein B1 (HMGB1) and airway inflammation in bronchial asthma and chronic obstructive pulmonary disease (COPD) patients. METHODS: A total of 57 patients with persistent asthma [per Global Initiative for Asthma (GINA) guidelines], 30 patients with stable COPD [stratified by Global Initiative for COPD (GOLD) status] and 20 control subjects were recruited. After completing an asthma control questionnaire, spirometry was performed before sputum induction. The ratio of forced expiratory volume in the first second (FEV(1))/predictive value (FEV(1)%Pre) and neutrophil differential count in induced sputum were recorded. The concentrations of HMGB1 in the supernatant of sputum were measured by ELISA (enzyme-linked immunosorbent assay). RESULTS: The sputum concentrations of HMGB1 in the asthmatics and COPD patients were significantly higher than those of the control subjects [(291 ± 55) and (511 ± 39) vs (61 ± 5) ng/L, all P < 0.01]. And they were significantly negatively correlated with FEV(1)%Pre in all subjects. The levels of HMGB1 in induced sputum of COPD patients were significantly higher than those of asthmatics and healthy controls (P < 0.01). No significant difference existed in the levels of HMGB1 between patients with eosinophilic and noneosinophilic asthma [(290 ± 55) vs (292 ± 54) ng/L, P > 0.05]. The HMGB1 levels with COPD stage II and stage III were significantly higher than those with stage I [(526 ± 29) and (541 ± 29) vs (471 ± 18) ng/L]. The differences of sputum neutrophil percentage were statistically significant in mild, moderate and severe asthma [(27 ± 2)%, (36 ± 4)%, (49 ± 4)%]. And the sputum levels of HMGB1 were significantly higher in the patients with moderate and severe asthma [(312 ± 14) vs (347 ± 11) ng/L]. And the levels of HMGB1 in asthmatic and COPD patients were positively correlated with neutrophil percentage. According to the multivariate analysis, neutrophil percentage and FEV(1)%Pre were independent predictors of sputum HMGB1, but not smoking, age, gender and eosinophilic percentage. CONCLUSION: HMGB1 may contribute to airway inflammation through its higher expression in bronchial asthma and COPD patients.