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1.
Thorac Cancer ; 3(3): 262-268, 2012 Aug.
Article in English | MEDLINE | ID: mdl-28920306

ABSTRACT

BACKGROUND: Lung cancers with mutations in the epidermal growth factor receptor (EGFR) gene respond well to treatment with EGFR inhibitors. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is considered a useful modality to obtain samples from the mediastinal and hilar lymph nodes. However, the EGFR gene status of EBUS-TBNA samples may not always match that of primary tumors. METHODS: In 14 node-positive patients diagnosed by EBUS-TBNA, EGFR mutation analysis results were compared between EBUS-TBNA samples and surgically removed primary tumors. EGFR mutation was screened with peptide nucleic acid-locked nucleic acid polymerase chain reaction (PNA-LNA PCR) clamp followed by direct sequence analysis. For one controversial case, gene mutation analyses were performed for the multiple micro-fractions of a metastatic lymph node, which exhibited the heterogeneous immunohistochemical features. RESULTS: EBUS-TBNA diagnosed one case of exon 21 point mutations, one case of exon 19 deletion, and 12 cases of wild-type EGFR. Results were consistent with those of surgically removed primary tumors in 13 of 14 cases. One case of wild-type EGFR diagnosed by EBUS-TBNA exhibited exon 21 point mutation in the surgically removed primary tumor. The metastatic lymph node targeted by EBUS-TBNA mostly consisted of cancer cells with wild-type EGFR; however, a minor component positive for thyroid transcription factor-1 (TTF-1) and surfactant-associated protein A (PE-10) exhibited EGFR mutation. CONCLUSION: The combination of EBUS-TBNA and PNA-LNA clamp is useful for EGFR mutation analysis. However, EGFR mutation status in EBUS-TBNA samples may not be consistent with that of the primary tumor when the tumor contains few EGFR mutations.

2.
Hypertens Res ; 30(10): 971-8, 2007 Oct.
Article in English | MEDLINE | ID: mdl-18049030

ABSTRACT

The combined effect of an angiotensin II type 1 receptor blocker and a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor on vascular lesion formation in the insulin-resistant state has not been examined. We tested whether or not combined treatment is superior to single-drug treatment for inhibiting vascular lesion formation in insulin-resistant rats. The rats were maintained on a fructose-rich diet for 4 weeks and then treated with olmesartan (1 mg/kg/day) and/or pravastatin (10 mg/kg/day) for 3 weeks. After 1 week of drug treatment, balloon injury of the carotid arteries was performed. Two weeks later, the injured arteries were harvested for morphometry and immunostaining. Olmesartan and pravastatin each modestly attenuated neointimal formation without significant changes in blood pressure or serum lipid levels. The combination of olmesartan and pravastatin significantly suppressed the neointimal formation compared with either monotherapy. The number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells was increased by olmesartan but not by pravastatin. Olmesartan and pravastatin each decreased the number of Ki-67-positive cells, which indicates cell proliferation, to the same extent. The combined treatment increased the number of TUNEL-positive cells but did not affect the number of Ki-67-positive cells. The combined treatment decreased the insulin level and increased the number of circulating endothelial progenitor cells. These results suggest that the combination of olmesartan and pravastatin is beneficial for the treatment of vascular diseases in the insulin-resistant state independently of blood pressure or cholesterol levels.


Subject(s)
Angioplasty, Balloon/adverse effects , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Carotid Artery Diseases/prevention & control , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Imidazoles/therapeutic use , Pravastatin/therapeutic use , Tetrazoles/therapeutic use , Animals , Apoptosis/physiology , Carotid Artery Diseases/pathology , Carotid Artery Diseases/physiopathology , Carotid Artery Injuries/etiology , Carotid Artery Injuries/pathology , Carotid Artery, Common/pathology , Cell Count , Cell Proliferation , Fructose/physiology , Immunohistochemistry , Insulin Resistance/physiology , Male , Rats , Rats, Sprague-Dawley , Stem Cells
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