Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for 80%-85% of all patients with lung cancer, the majority of patients with lung cancer at the time of diagnosis is in the advanced stage. The development of target therapy based on has changed the mode of treatment in patients with advanced NSCLC. In NSCLC, epidermal growth factor receptor mutation (EGFR) fusion with echinoderm microtubule-associated protein-like4-anaplastic lymphoma kinase (EML4-ALK) has been shown to be a powerful biomarker. It is well known that KRAS is also NSCLC one of the most common mutations in oncogenes, although more than 20 years ago KRAS mutation was found in NSCLC. At present, although there are many drugs used to treat NSCLC patients with KRAS mutation, there is no selective or specific inhibitor for the direct elimination of KRAS activity. NSCLC patients with KRAS mutation have poor responsiveness to most systemic therapy. However, individualized therapy for activated signaling pathways with targeted drugs has a good effect on the prognosis of NSCLC patients with KRAS mutation. In addition, the prognostic and predictive role of KRAS mutation in NSCLC remains unclear. In this review, we focus on the research progress of NSCLC with KRAS mutation, including molecular biology, clinicopathological features, prognosis and prediction of KRAS mutation, which will help to improve the understanding of NSCLC in KRAS mutation.
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Animals ; Carcinoma, Non-Small-Cell Lung ; enzymology ; genetics ; Humans ; Lung Neoplasms ; enzymology ; genetics ; Mutation ; Proto-Oncogene Proteins p21(ras) ; genetics

OBJECTIVETo investigate the expression of tripartite-motif protein 25 (TRIM25) and pyruvate kinase M2 (PKM2) protein in non-small cell lung cancer (NSCLC) and explore their role in the occurrence and progression of NSCLC.

METHODSThe expressions of TRIM25 and PKM2 protein were detected in 60 NSCLC specimens and 20 adjacent normal lung tissue (>5 cm from the lesions) with immunofluorescence histochemical method and in 10 fresh specimens of NSCLC with Western blotting. The results were analyzed in relation with the clinicopathological features of the patients.

RESULTSThe positivity rates of TRIM25 expression was 45% in the 60 lung carcinoma specimens, significantly higher than that in the 20 normal lung tissues (10%, P=0.005). TRIM25 protein was expressed in 28.6% of lung adenocarcinoma tissues and in 59.4% of squamous carcinoma tissues (P=0.017). TRIM25 protein expression was positively correlated with the TNM stages and lymph node metastasis of NSCLC (P<0.05). The expressions of PKM2 protein in 60 cases of lung carcinoma was 73.3%,while in 20 cases of normal lung tissues the expressions was 30%(P=0.001). The positivity rates of PKM2 expression differed significantly between lung adenocarcinoma and squamous carcinoma (57.1% vs 87.5%, P=0.008). An inverse correlation was noted between TRIM25 and PKM2 expressions (P=0.026).

CONCLUSIONTRIM25 and PKM2 protein may participate in the occurrence and progression of NSCLC, and their expressions are inversely correlated.

Adenocarcinoma ; enzymology ; Carcinoma, Non-Small-Cell Lung ; enzymology ; Carcinoma, Squamous Cell ; enzymology ; Carrier Proteins ; metabolism ; Humans ; Lung ; pathology ; Lung Neoplasms ; enzymology ; Lymphatic Metastasis ; Membrane Proteins ; metabolism ; Thyroid Hormones ; metabolism ; Transcription Factors ; metabolism ; Tripartite Motif Proteins ; Ubiquitin-Protein Ligases ; metabolism

The effects of thyroid hormone on hepatic and gastric alcohol dehydrogenase (ADH) activities (nM of NADH/min/mg of cytosolic protein) have been investigated in male Sprague Dawley rats treated with thyroxine (1 mg/kg, po) for 14 days. Whereas hepatic ADH activity in thyroxine-treated rats decreased by 61.3% of control rats (26.4 vs 43.2, p<0.001), gastric ADH activity increased by 262.9% of control rats (4.9 vs 1.9, p<0.001). As for the activities of the lung and kidney, thyroxine treatment did not produce any statistically significant changes. These data suggest that thyrotoxicosis causes a decrease of hepatic alcohol metabolism, and that the increase of gastric ADH activity in thyrotoxic rats can partly restore the first-pass metabolism of ethanol.
Alcohol Dehydrogenase/*metabolism ; Animal ; Gastric Mucosa/enzymology ; Kidney/enzymology ; Liver/drug effects/*enzymology ; Lung/enzymology ; Male ; Rats ; Rats, Sprague-Dawley ; Stomach/drug effects/*enzymology ; Thyrotoxicosis/chemically induced/metabolism ; Thyroxine/administration & dosage/*metabolism/pharmacology

We assessed the effects of furan and lycopene on the histopathological and biochemical changes on lungs, body and lung weights, and food consumption of rats. Furan and diabetes caused histopathological changes, increment in malondialdehyde levels, and decrease in antioxidant enzyme activities. Lycopene showed a protective effect against these damages, except for glutathione-S-transferase and glutathione peroxidase activities. Consequently, furan and diabetes resulted in lung toxicity. Our findings demonstrate that furan treatment resulted in more alterations in histology and biochemical parameters in diabetic rats and lycopene showed protective effects against these alterations.
Animals ; Antioxidants ; pharmacology ; Carotenoids ; pharmacology ; Diabetes Mellitus, Experimental ; enzymology ; pathology ; Furans ; toxicity ; Lung ; drug effects ; enzymology ; pathology ; Male ; Rats, Wistar

OBJECTIVETo investigate DNA-dependent protein kinase catalytic subunit (DNA-PKcs) content and activity in lung adenocarcinoma cell lines and its correlation with radiosensitivity.

METHODSThe content and activity of DNA-PKcs were analyzed in two lung adenocarcinoma cell lines A549 and H1299 by Western blotting and the Signa TECT DNA-PK assay kit. The dose-survival relationship for two cell lines was analyzed using clonogenic formation assay.

RESULTSA549 was more radiosensitive than H1299. The survival fractions at 2 Gy (SF2) were 0.7412 in A549 cell line and 0.2473 in H1299 cell line. The content of DNA-PKcs was significantly higher in A549 cells than in H1299 cells (t=10.37, P<0.001). The integrated optical densities were 3.29-/+0.44 in A549 cells and 0.50-/+0.17 in H1299 cells. DNA-PKcs activities in A549 and H1299 cells were 8.29-/+1.37 and 2.47-/+1.09, respectively, showing a significant difference between them (t=5.76, P=0.005).

CONCLUSIONDNA-PKcs is an important factor to affect the radiosensitivity of lung adenocarcinoma cell lines.

Adenocarcinoma ; enzymology ; pathology ; Calcium-Binding Proteins ; genetics ; metabolism ; Cell Line, Tumor ; Humans ; Lung Neoplasms ; enzymology ; pathology ; Radiation Tolerance

OBJECTIVETo measure peripheral serum levels of matrix metalloproteinase 9 (MMP9) and matrix metalloproteinase 19 (MMP19) in patients with pneumoconiosis, and to investigate their feasibility as potential biomarkers for pneumoconiosis.

METHODSNinety-eight male patients with pneumoconiosis (49 patients in phase I, 36 patients in phase II, and 13 patients in phase III) were enrolled as subjects, which included 41 patients with silicosis and 57 patients with coal workers' pneumoconiosis. Ninety-eight healthy male physical examinees were used as controls. A fasting blood sample (3 ml) was collected from the peripheral venous blood of each patient or control, and the serum was separated from the blood sample. The expression levels of MMP9 and MMP19 in serum were measured by enzyme-linked immunosorbent assay.

RESULTSSerum levels of MMP9 and MMP19 in patients with silicosis or coal workers' pneumoconiosis were significantly lower than those in the control group (P < 0.05). Serum levels of MMP19 in patients with silicosis were significantly higher than those in patients with coal workers' pneumoconiosis (P < 0.05). Serum levels of MMP19 in patients exposed to dust for less than 7 years were significantly higher than those in patients exposed to dust for more than 20 years (P < 0.05). There were no significant differences in serum levels of MMP9 and MMP19 between patients with different levels of pulmonary function impairment (P > 0.05). Serum expression levels of MMP9 and MMP19 were positively correlated with each other in both patients with pneumoconiosis and those in the control group (P < 0.05). The serum expression level of MMP9 was negatively correlated with the stage of pneumoconiosis (P < 0.05).

CONCLUSIONSerum MMP9 and MMP19 may be used as potential biomarkers for pneumoconiosis.

Anthracosis ; enzymology ; Biomarkers ; Coal Mining ; Dust ; Humans ; Lung ; Male ; Matrix Metalloproteinase 9 ; blood ; Matrix Metalloproteinases, Secreted ; blood ; Occupational Exposure ; Pneumoconiosis ; blood ; enzymology ; Silicosis ; enzymology

OBJECTIVETo investigate the changes in serum protease and cytokine in patients with silicosis, tuberculosis, and lung cancer.

METHODSSerum samples of patients with silicosis, tuberculosis, and lung cancer were collected. The variation trends of the expression of granzyme A, cathepsin G, apolipoprotein A, and interferon-β (IFN-β) were analyzed using enzyme-linked immunosorbent assay.

RESULTSThe concentration of apolipoprotein A of the silicosis group was 200 µg/ml, significantly higher than those of the tuberculosis and lung cancer groups (P < 0.05), and the lung cancer group had a significantly higher concentration of apolipoprotein A compared with the tuberculosis group (P < 0.05). The silicosis group had significantly higher expression of cathepsin G compared with the tuberculosis and lung cancer groups (P < 0.05), and the tuberculosis group and lung cancer group showed no significant difference in the concentration of cathepsin G (P > 0.05). The tuberculosis group had a significantly higher concentration of granzyme A than the silicosis and lung cancer groups (P < 0.05), and the silicosis group and lung cancer group had similar protein concentration trends (P > 0.05). The tuberculosis group and lung cancer group had significantly higher concentration of IFN-β compared with the silicosis group (P < 0.05), and the tuberculosis group and lung cancer group showed no significant difference in IFN-β concentration (P > 0.05).

CONCLUSIONThis study may offer diagnostic markers for the clinical diagnosis of silicosis, tuberculosis, and lung cancer, and could provide a basis for the research, as well as potential molecular targets for the diagnosis and treatment of these diseases.

Biomarkers ; Cathepsin G ; metabolism ; Cytokines ; blood ; Endopeptidases ; blood ; Enzyme-Linked Immunosorbent Assay ; Granzymes ; metabolism ; Humans ; Interferon-beta ; metabolism ; Lung Neoplasms ; enzymology ; Silicosis ; enzymology ; Tuberculosis ; enzymology

OBJECTIVETo evaluate the change in protein expression of peroxiredoxin I (Prx I) during pulmonary fibrosis among rats exposed to silica dust and to investigate the role of Prx I in pulmonary fibrosis.

METHODSNinety male Wistar rats were randomly divided into control group (n = 60) and experimental group (n = 30). The control group received intratracheal perfusion of saline (1 ml), while the experimental group received intratracheal perfusion of suspension of silica dust (50 mg/ml) to establish a rat model of silicosis. At 1, 2, 3, 4, 6, or 8 weeks after treatment, 10 rats in control group and 5 rats in experimental group were sacrificed. The lung tissues were collected for conventional pathological observation. The protein expression of Prx I at each time point was measured by immunohistochemistry and Western blot.

RESULTSAmong the rats exposed to silica dust, Prx I was seen in the form of brown particles that were mainly distributed in the alveolar septa and the cytoplasm of alveolar epithelial cells, macrophages, vascular endothelial cells, and smooth muscle cells around the blood vessels and tracheae. The control group showed weak protein expression of Prx I, and the experimental group had significantly higher protein expression of Prx I than the control group at all time points (P < 0.05). In the experimental group, the protein expression of Prx I was upregulated significantly at 1 and 2 weeks and decreased at 3∼8 weeks.

CONCLUSIONThe change in protein expression of Prx I may be one of the important causes of the onset and development of pulmonary fibrosis in rats exposed to free silica.

Animals ; Disease Models, Animal ; Lung ; enzymology ; pathology ; Male ; Peroxiredoxins ; metabolism ; Pulmonary Fibrosis ; enzymology ; pathology ; Rats ; Rats, Wistar ; Silicon Dioxide ; toxicity ; Silicosis ; enzymology ; pathology

BACKGROUND AND OBJECTIVEIt has been proven that telomerase activation correlates with the carcinogenesis, aggressiveness and turnover of lung cancer. Telomerase is one of the improtant molecular biomarkers for diagnosis and targeting therapy in lung cancer. The aim of this study is to investigate the diagnostic value of the combined determination of telomerase activity in induced sputum, pleural effusion and fiberobronchoscopic biopsy in lung cancer patients.

METHODSThe technique of TRAP (telomeric repeat amplification protocal)-PCR-ELISA was employed to detect telomease levels of induced sputum, pleural effusion and fiberobronchoscopic biopsy in 80 lung cancer patients with pleural effusion and 50 benign pulmonary disease patients with pleural effusion.

RESULTSTelomemse levels of induced sputum, pleural effusion and fiberobronchoscopic biopsy were all significantly higher in patients with lung cancer than those with benign pulmonary disease (P < 0.001). There was no significant difference in the level of telomerase activity between different pathologic types (P > 0.05). The sensitivity of induced sputum, pleural effusion and fiberobronchoscopic biopsy were 62.5% (50/80), 46.3% (37/80) and 60.0% (48/80), respectively. The specificity were 72.0% (36/50), 66.0% (33/50) and 70.0% (35/50), respectively. The overall accuracy were 66.2% (86/130), 53.8% (70/130) and 63.8% (83/130), respectively. The sensitivity, specificity and overall accuracy of combined induced sputum, pleural effusion and fiberobronchoscopic biopsy were 85.0% (68/80), 78.0% (39/50) and 82.3% (107/130), respectively. The sensitivity of telomease level in combined detection for diagnosis of lung cancer was much higher than that in single sample detection (P < 0.01).

CONCLUSIONThe sensitivity of telomease activity in combined three samples was the highest. It can further improve the accuracy for the diagnosis of lung cancer with pleural effusion.

Aged ; Biopsy ; Bronchoscopy ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Lung Neoplasms ; diagnosis ; enzymology ; Male ; Middle Aged ; Pleural Effusion ; enzymology ; Polymerase Chain Reaction ; Sputum ; enzymology ; Telomerase ; metabolism

OBJECTIVETo investigate the frequency of anaplastic lymphoma kinase (ALK) expression in non-small cell lung cancer (NSCLC) patients and its correlation with the clinicopathologic features.

METHODSALK immunohistochemistry and ALK fluorescent in situ hybridization (FISH) were performed on formalin-fixed, paraffin-embedded tissue in 100 cases of NSCLCs between 2011 and 2013. Relevant clinicopathologic data were collected and correlated with ALK expression.

RESULTSAll patients with immunohistochemical score of 3 (n = 12) were FISH-positive and all patients with score of 0 (n = 78) were FISH-negative. Among patients with immunohistochemical scores of 1 and 2, 2/3 and 6/7 were FISH-positive, respectively. The sensitivity and specificity of ALK immunohistochemistry with intensity score of 1 or more were 100% and 98%, respectively. Invasive mucinous adenocarcinoma, solid or acinar growth pattern, presence of mucous cells (signet-ring cells or goblet cells), extracellular mucus and lack of significant nuclear pleomorphism characterized ALK-rearranged cancer.

CONCLUSIONSALK-rearranged cancers possess specific histological features. Immunohistochemistry can be used as a routine test for screening ALK-positive cases in advanced NSCLC, and FISH testing should be used to confirm ALK translocation for patients with tumors showing staining for ALK by immunohistochemistry. All of these can help physicians identify patients who may benefit from targeted therapy.

Carcinoma, Non-Small-Cell Lung ; enzymology ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lung Neoplasms ; enzymology ; Male ; Paraffin Embedding ; Receptor Protein-Tyrosine Kinases ; metabolism ; Sensitivity and Specificity