Malignant pleural effusion (MPE) and blood samples can be used as a practical source for detection of epidermal growth factor receptor (EGFR) mutations in patients with advanced non-small cell lung cancer. We compared EGFR mutation status of cell blocks, cell-free fluid of MPE, and plasma from patients with lung adenocarcinoma. We obtained paired samples of MPE and plasma from 14 pathologically-confirmed lung adenocarcinoma patients. Peptide nucleic acid (PNA)-mediated real-time polymerase chain reaction (RT-PCR) clamping was performed for determination of EGFR mutation status. EGFR mutations were detected in five (35.7%) cell blocks of MPE, which showed results identical to those of the corresponding cell-free fluid, whereas mutations were detected in the plasma of only two (40.0%) of the five patients. Of seven patients treated with EGFR tyrosine kinase inhibitors (TKIs), EGFR mutations were detected in cell blocks, cell-free fluid of MPE, and plasma for only one of the four patients who responded to EGFR TKIs, while mutations were detected only in cell blocks of MPE and cell-free fluid of the three remaining patients. Our results suggest that detection of EGFR mutations in cell-free pleural fluid from lung adenocarcinoma patients using highly sensitive methods may be feasible, but that analysis of free plasma may lead to undetected mutations and misdiagnosis.

The human ELAV(embryonic lethal abnormal vision)-like protein HuR stabilizes a certain group of cellul ar mHNAs that contain AU- rich elements in their 3’ - untranslated region , To test the significance of HuR in carcinogenesis of head and neck squamous cell carcinomas(HNSCCs), we have investigated HuH expression from 32 benign epithelial lesions , 14 prema lignant epitheli al lesions and 80 HNSCCs, There were two different staining patterns of HuR in HNSCCs : nuclear expression was seen in 78 7% (63 of 80) 01' cases; and an additional cyto plasmic expression was seen in 28, 7%(23 of 80) 01 cases, Nuclear expression of HuR was s ignificantly increased in premalignant lesions and HNSCCs, whereas increased cytoplasπli c expression of HuR was only observed in HNSCCs Cytoplasmic HuR expression was significantly increased in pa tients of HNSCC younger than 60 yea rs , Al though there was no significant correlation between a natomic s ites of HNSCCs and HuR express ion , cyto plasmic HuR expression was highly increased in HNSCCs of larynx, There was no significant co rrela tion between HuR expression and other clinicopathological parameters such as histological type‘ tumor s ize‘ 0 1' n odal s tatus , ln conclusion, this study s uggests that overexpression of HuR in HNSCCs may be part of a regula tory pathway tha t co ntro ls the mHNA stability 0 1' several important targets in carcinogenesis of HNSCCs

1,1- Bis(3’-indolyl)-l-(p-methoxyphenyl)methane (DIM- C- pPhOCH.3) is a methylenc - substituted diindolylmethanes (C-DIM) ana log that acti vates the orphan receptOl‘ nerve growth factor-induced-B (NGFI-B, Nur77) , RNA inteference studies with small inhibitory RNA for Nur77 demonstrate that DIM-C-pPhOCH:J induces Nur77-dependent and - independent apoptosis, and this study has focused on delineating the Nur77-independent proapoptotic pathways induced by the C-DIM analog DIM-C-pPhOCH3 induced caspase-dependent apoptosis in RKO colon cancer cells through decreased mitochondrial membrane potential which is accompanied by increased mitochondrial bax/bcl-2 ratios and release of cytochrome c into the cytosol DlM-C一pPhOCH.3 also induced phosphatidylinositol-3-kinase-dependent activation of early growth response gene-l whi ch, in turn, induced expression of the proapoptotic nonsteroidal anti-inflammatory drug- activated gene-l (NAG- l) in colon tumors in athyrnic nude mice bearing RKO cells as xenografts, DIM-C-pPhOCH.3 also activated the extrinsic apoptosis pathway through increased phosphorylation of c- jun N-terminal kinase which, in turn, activated C/EBP homologous transcription factor (CHOP) and death receptor 5 (DR5) , Thus, the effectiveness of DIM-C-pPhOCH.3 as a tumor growth inhibitor is through activation of Nur77-dependent and -independent pathways