BACKGROUND: Advanced epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma had a high overall incidence of brain metastasis during the full course, and local brain radiotherapy combined with systemic targeted therapy may be a better strategy. This study aimed to identify the prognostic factors of EGFR-mutant brain-metastatic lung adenocarcinoma patients who received EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in combination with gamma knife radiosurgery. METHODS: Retrospective analysis of EGFR-mutant lung adenocarcinoma patients with brain metastases which developed at initial diagnosis or during EGFR-TKIs treatment period were performed. Intracranial progression free survival (PFS) was statistically analyzed between different subgroups to find out the prognostic factors including gender, age, smoking history, extracranial metastasis, EGFR mutation type, size and number of intracranial lesions, carcino-embryonic antigen (CEA) level, lung-molGPA score and so on. RESULTS: A total of 74 EGFR-mutant brain-metastatic lung adenocarcinoma patients were enrolled in this study, with median intracranial PFS of 14.7 months. One-year intracranial-progression-free rate was 58.5%, and two-year rate was 22.2%. Univariate survival analysis showed that patients with lower CEA level at initial diagnosis (<10 ng/L)(16.9 months vs 12.6 months, P=0.012) and smaller intracranial lesions (<2 cm)(15.4 months vs 10.8 months, P=0.021) and higher lung-molGPA score (>3)(15 months vs 12.6 months, P=0.041) were prone to have a superior intracranial PFS. Multivariate analysis showed that CEA≥10 ng/mL and intracranial lesion≥2 cm were the independent risk factors of intracranial PFS. CONCLUSIONS EGFR-TKIs in combination with gamma knife radiosurgery was an efficient treatment option to control the cranial tumor lesion. CEA≥10 μg/L at initial diagnosis and intracranial lesion≥2 cm were the risk factors of EGFR-mutant brain-metastatic lung adenocarcinoma patients receiving EGFR-TKIs in combination with gamma knife radiosurgery.
Adenocarcinoma of Lung ; drug therapy ; pathology ; radiotherapy ; therapy ; Adult ; Aged ; Brain Neoplasms ; secondary ; Combined Modality Therapy ; ErbB Receptors ; antagonists & inhibitors ; genetics ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Prognosis ; Protein Kinase Inhibitors ; pharmacology ; therapeutic use ; Radiosurgery ; Retrospective Studies

Although mounting evidence indicates the involvement of galectin-3 in cancer progression and metastasis, the underlying molecular mechanisms remain largely unknown. In this study, we investigated the effect and possible mechanism of galectin-3 on the migration and invasion of B16F10, a metastatic melanoma cell line, in which galectin-3 and matrix metalloproteinase-1 (MMP-1) were both found to be highly expressed. Knockdown of galectin-3 with specific siRNA reduced migration and invasion, which was associated with reduced expression of MMP-1. To further investigate the underlying mechanism, we examined the effect of galectin-3 knockdown on the activity of AP-1, a transcriptional factor regulating MMP-1 expression. We found that galectin-3 directly interacted with AP-1 and facilitated the binding of this complex to the MMP-1 promoter that drives MMP-1 transcription. Moreover, silencing of galectin-3 inhibited binding of fra-1 and c-Jun to promoter sites of MMP-1 gene. Consistent with these in vitro findings, our in vivo study demonstrated that galectin-3 shRNA treatment significantly reduced the total number of mouse lung metastatic nodules. Taken together, galectin-3 facilitates cell migration and invasion in melanoma in vitro and can induce metastasis in vivo, in part through, regulating the transcription activity of AP-1 and thereby up-regulating MMP-1 expression.
Animals ; Binding Sites/genetics ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Galectin 3/genetics/*metabolism ; JNK Mitogen-Activated Protein Kinases/metabolism ; Lung Neoplasms/drug therapy/genetics/*secondary ; Matrix Metalloproteinase 1/*genetics/*metabolism ; Melanoma, Experimental/*metabolism/*pathology/secondary ; Mice ; Mice, Inbred C57BL ; NIH 3T3 Cells ; Neoplasm Metastasis ; Promoter Regions, Genetic ; Proto-Oncogene Proteins c-fos/metabolism ; RNA Interference ; RNA, Small Interfering ; Transcription Factor AP-1/*genetics/metabolism ; Transcription, Genetic ; Transcriptional Activation

BACKGROUND AND OBJECTIVEThere is a mounting evidence of the role of HER2 overexpression inpatients with gastric cancer, and it has been solidly correlated with poor outcomes and more aggressive diseases. This study was to investigate the relationship between the expression of HER2/neu and the clinical characteristics of advanced gastric carcinomas, including survival.

METHODSThe clinical data of 83 patients admitted in Cancer Hospital, Chinese Academy of Science, from 2006 to 2008 were reviewed. The HER2/neu status in 83 advanced gastric carcinomas was evaluated using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). The survival rate was calculated by Kaplan-Meier method and the log-rank test using SPSS13.0 software.

RESULTSThe median age of the patients was 60 years and the male-to-female ratio was 2.95:1. HER2/neu overexpression (2+ and 3+) and amplification were found in 25 (30.1%) and 29 (34.9%) advanced gastric carcinomas, respectively. HER2/neu amplification/overexpression was associated with worse survival in patients with advanced gastric carcinoma. The median survival of the patients without HER2/neu amplification was 12.6 months and that of those with HER2 amplification was 5.5 months.

CONCLUSIONSHER2/neu status may be a clinical predictor of prognosis in advanced gastric cancer patients.

Adenocarcinoma ; drug therapy ; genetics ; metabolism ; pathology ; secondary ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Signet Ring Cell ; drug therapy ; genetics ; metabolism ; pathology ; secondary ; Female ; Gene Amplification ; Gene Expression Regulation, Neoplastic ; Genes, erbB-2 ; Humans ; Liver Neoplasms ; secondary ; Lung Neoplasms ; secondary ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Receptor, ErbB-2 ; metabolism ; Stomach Neoplasms ; drug therapy ; genetics ; metabolism ; pathology ; Survival Rate

OBJECTIVETo investigate the correlation of the mRNA expression level of excision repair cross-complementing group 1 (ERCC1) gene with clinicopathological parameters and clinical outcome in patients with non-small cell lung cancer (NSCLC) receiving platinum-based chemotherapy.

METHODSThe mRNA expression of ERCC1 in formalin-fixed paraffin-embedded primary tumor specimens was measured by real-time quantitative reverse transcriptase polymerase chain reaction. The association between ERCC1 expression levels and clinicopathological parameters in NSCLC patients was analyzed.

RESULTSThe median value of ERCC1 mRNA expression level compared with beta-actin in tumor specimens of 61 NSCLC patients was 0.48. There was no correlation between ERCC1 expression and clinicopathological parameters. Patients with low expression of ERCC1 mRNA (less than 0.35, 0.28, respectively) had a significantly longer median time to progression (TTP) (14.3 vs. 8.0 months, P = 0.028) and overall survival (OS) (28.4 vs. 12.9 months, P = 0.0064) than those with high expression. Multivariate analysis showed that a low ERCC1 mRNA expression was an independent factor for OS.

CONCLUSIONOur findings suggest that intratumoral ERCC1 mRNA expression level, although is uncorrelated with clinicopathological parameters, is an independent predictive marker for survival of the patients with NSCLC receiving platinum-based chemotherapy, and may provide critical information for personalized chemotherapy.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bone Neoplasms ; secondary ; Brain Neoplasms ; secondary ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; metabolism ; pathology ; secondary ; Cisplatin ; administration & dosage ; DNA-Binding Proteins ; genetics ; metabolism ; Disease-Free Survival ; Endonucleases ; genetics ; metabolism ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; drug therapy ; metabolism ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Paraffin Embedding ; Platinum ; administration & dosage ; Proportional Hazards Models ; RNA, Messenger ; metabolism ; Survival Rate