Objective To study the genes which simultaneously participate in different carcinogenesis progression in lung adenocarcinoma for biomarkers identification. Methods 10 lung adenocarcinoma samples including pathologic stage Ⅰ,Ⅱ,Ⅲ were chosen for experiment and their matched normal tissues for control. After hybridization on 20 slides of microarray with 13824 genes, we analyze the expression profiles combined with pathologic stage and clinical prognosis by data mining. The genes differentially coexpressed in different stage and different prognosis samples were the target. Results 119 genes were identified. Among these targets, 26 genes have known to be related to lung cancer, 46 genes were unreported and 47 gene were new. Conclusions The 119 genes were very important during cancer occurrence and development and were the candidate biomarkers in lung adenocarcinoma.

The expression, amplification and rearrangement of c-myc and c-erbB-2 genes in thyroid tumor were studied. 32P-dATP-labelled probes of c-myc, c-erbB-2 and v-sis DNA fragments were used to hybridise with the cellular total RNA. We found that c-myc and c-erbB-2 oncogenes were expressed in all samples. The levels of c-myc RNA were three-to eleven-fold higher in 9 out of 15 cancer samples when compared with that in normal tissues. In 7 of 15 cancer samples, c-erbB-2 gene was overexpressed 10~50 times higher than normal. No v-sis RNA was detected in all the samples. Southern blot hybridisation showed that rearrangement of c-myc oncogene were observed in 4 cancer samples, of which one showed a 150-fold amplification of c-myc gene. No amplification or rearrangement of c-erbB-2 gene was detected. These data indicate that the activat.:on of c-myc and c-erbB-2 oncogenes may contribute to the development and/or maintenance of the malignant phenotype of the thyroid carcinomas.

Objective To investigate the significance of expressions of neutrophil and lymphocyte CD11b in children with severe pneumonia.Methods Expressions of neutrophils and lymphocytes CD11b were measured by flow cytometry in 36 children with severe pneumonia( severe pneumonia group),compared with 35 children with mild pneumonia ( mild pneumonia group) and 30 healthy children ( control group).Results In acute stage,expressions of neutrophil CD11b in severe pneumonia group and mild pneumonia group were (90.67 ± 7.03 ) ％ and ( 84.03 ± 5.08 ) ％,respectively,both of which were higher than that in control group [ ( 69.32 ± 5.72 ) ％ ] ( P ＜ 0.05 ).Furthermore,in acute stage,expression of neutrophils CD11b in severe pneumonia group was higher than that in mild pneumonia group (P ＜ 0.05 ).In recovery stage,expressions of neutrophil CD11b in children with severe pneumonia and mild pneumonia were(72.68 ±2.07 ) ％ and (71.45 ± 3.21 ) ％,respectively,which were both lower than those in acute stage ( P ＜ 0.05 ).In acute stage,expression of lymphocyte CD11b of children with severe pneumonia was ( 13.35 ± 6.52 )％,which was lower than that of mild pneumonia group [ ( 19.19 ± 6.47 ) ％ ] ( P ＜ 0.05 ),however,no significant difference was found between severe pneumonia group and control group [ ( 12.42 ± 6.43 ) ％ ] ( P ＞0.05).In recovery period,there was no significant difference in the expression of lymphocytes CD11b between severe pneumonia group [ ( 13.37 ± 4.88 ) ％ ] and mild pneumonia group [ ( 13.78 ± 4.53 ) ％ ] ( P ＞0.05).Conclusion Expressions of neutrophil and lymphocyte CD11 b participate in the pathogenesis of severe pneumonia.Detection of CD11b expression is helpful to diagnose severe pneumonia and predict the prognosis.

BACKGROUNDTo explore the experience of gefitinib molecular target therapy for Chinese patients with non-small cell lung cancer (NSCLC).

METHODSThe unpublished data of gefitinib for advanced NSCLC in 7 hospitals were collected. The detailed data from Guangdong Provincial People's Hospital were analyzed.

RESULTSA total of 282 patients with advanced NSCLC was treated with gefitinib from July 2001 to December 2003. Response rate was 22.2%-47.7%, disease control rate 62.6%-81.8%. No severe side effects were surveyed.

CONCLUSIONSGefitinib can be used safely and effectively in Chinese patients with advanced NSCLC.

Carcinoma, Non-Small-Cell Lung ; classification ; therapy ; China ; Humans ; Lung Neoplasms ; classification ; therapy ; Practice Guidelines as Topic ; Receptor Protein-Tyrosine Kinases ; metabolism

Excessive microglial activation and subsequent neuroinflammation lead to synaptic loss and dysfunction as well as neuronal cell death, which are involved in the pathogenesis and progression of several neurodegenerative diseases. Thus, the regulation of microglial activation has been evaluated as effective therapeutic strategies. Although dieckol (DEK), one of the phlorotannins isolated from marine brown alga Ecklonia cava, has been previously reported to inhibit microglial activation, the molecular mechanism is still unclear. Therefore, we investigated here molecular mechanism of DEK via extracellular signal-regulated kinase (ERK), Akt and nicotinamide adenine dinuclelotide phosphate (NADPH) oxidase-mediated pathways. In addition, the neuroprotective mechanism of DEK was investigated in microglia-mediated neurotoxicity models such as neuron-microglia co-culture and microglial conditioned media system. Our results demonstrated that treatment of anti-oxidant DEK potently suppressed phosphorylation of ERK in lipopolysaccharide (LPS, 1 microg/ml)-stimulated BV-2 microglia. In addition, DEK markedly attenuated Akt phosphorylation and increased expression of gp91(phox), which is the catalytic component of NADPH oxidase complex responsible for microglial reactive oxygen species (ROS) generation. Finally, DEK significantly attenuated neuronal cell death that is induced by treatment of microglial conditioned media containing neurotoxic secretary molecules. These neuroprotective effects of DEK were also confirmed in a neuron-microglia co-culture system using enhanced green fluorescent protein (EGFP)-transfected B35 neuroblastoma cell line. Taken together, these results suggest that DEK suppresses excessive microglial activation and microglia-mediated neuronal cell death via downregulation of ERK, Akt and NADPH oxidase-mediated pathways.
Adenine ; Cell Death* ; Cell Line ; Coculture Techniques ; Culture Media, Conditioned ; Down-Regulation ; Microglia ; NADP* ; NADPH Oxidase ; Neuroblastoma ; Neurodegenerative Diseases ; Neurons* ; Neuroprotective Agents ; Niacinamide ; Phosphorylation ; Phosphotransferases ; Reactive Oxygen Species

Rearranged during transfection (RET) fusions are found in 0.7% to 2% of non-small cell lung cancer (NSCLC). Fusions between RET gene and other domains represent the distinct biological and clinicopathological subtypes of NSCLC. Recent years have witnessed the remarkable advancement of RET fusion-positive advanced NSCLC therapy. Conventional chemotherapy produced moderate clinical benefits. Prior to the introduction of targeted therapy or in the context of unavailability, platinum-based systemic regimens are initial therapy options. Immunotherapy predicted minimal response in the presence of RET fusions while currently available data have been scarce, and the single-agent immunotherapy or in combination with chemotherapy regimens are not recommended as initial systemic therapy in this population. The repurpose of multi-target kinase inhibitors in patients with RET fusion-positive NSCLC showed encouraging therapeutic activity, with only cabozantinib and vandetanib being recommended as initial or subsequent options under certain circumstances. However, there are still unmet clinical needs. Pralsetinib and selpercatinib have been developed as tyrosine kinase inhibitors (TKI) selectively targeting RET variation of fusions or mutations, and both agents significantly improved the prognosis of patients with RET fusion-positive NSCLC. Pralsetinib and selpercatinib have been established as preferred first-line therapy or subsequent therapy options. As observed with other TKIs treatment, resistance has also been associated with RET targeted inhibition, and the acquired resistance eventually affect the long-term therapeutic effectiveness, leading to limited subsequent treatment options. Therefore, it is essential to identify resistance mechanisms to TKI in RET fusion-positive advanced NSCLC to help reveal and establish new strategies to overcome resistance. Here, we review the advances in the treatment of RET fusion-positive advanced NSCLC.
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Carcinoma, Non-Small-Cell Lung/genetics* ; Humans ; Lung Neoplasms/genetics* ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; Proto-Oncogene Proteins c-ret/genetics*