Int J Clin Exp Patho
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Int J Clin Exp Patho · Jan 2013
Screening for EGFR and KRAS mutations in non-small cell lung carcinomas using DNA extraction by hydrothermal pressure coupled with PCR-based direct sequencing.
EGFR and KRAS mutations correlate with response to tyrosine kinase inhibitors in patients with non-small cell lung carcinoma (NSCLC). We reported a hydrothermal pressure method of simultaneous deparaffinization and lysis of formalin-fixed paraffin embedded (FFPE) tissue followed by conventional chaotropic salt column purification to obtain high quality DNA for mutation analysis using PCR-base direct sequencing. This study assessed the feasibility of using this method to screen for exons 18-21 of EGFR and exon 2 of KRAS gene mutations in surgical resection and core needle biopsy specimens from 251 NSCLC patients. ⋯ Twenty-one patients had multiple mutations at different exons of EGFR, in which seventeen patients had deletions in exon 19. KRAS mutations were found in 18 (7.2%) patients (15 in adenocarcinoma, 2 in squamous cell carcinoma and one in NSCLC-not otherwise specified), including an uncommon substitution G13C. Deparaffinization and lysis by hydrothermal pressure, coupled with purification and PCR-based sequencing, provides a robust screening approach for EGFR and KRAS mutation analysis of FFPE tissues from either surgical resection or core needle biopsy in clinical personalized management of lung cancer.
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Int J Clin Exp Patho · Jan 2013
Clinical characteristics and treatment of angiomatous meningiomas: a report of 27 cases.
Angiomatous meningioma (AM) is a rare histological variant of meningioma. Twenty seven patients (14 male and 13 female) with angiomatous meningioma were treated in our institution. Their clinical presentation, neuroimaging studies, treatment and follow-up were investigated. ⋯ Gross total resection is still the treatment of choice. These patients with residual tumor after surgery can benefit from radiation therapy. Overall, the prognosis of AMs are as good as other benign meningiomas.
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Int J Clin Exp Patho · Jan 2013
Association of the brain-derived neurotrophic factor gene G196A rs6265 polymorphisms and the cognitive function and clinical symptoms of schizophrenia.
This study aimed to explore the association between BDNF G196A gene rs6265 polymorphisms and the cognitive function and clinical symptoms of schizophrenia. ⋯ BDNF G196A gene rs6265 polymorphism is not associated with the cognitive function but with the clinical symptoms of schizophrenia.
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Int J Clin Exp Patho · Jan 2013
Inhibition of GAP-43 by propentofylline in a rat model of neuropathic pain.
Neural plasticity within the spinal nociceptive network may be fundamental to the chronic nature of neuropathic pain. The relation of growth-associated protein-43 (GAP-43), a protein involved in the nerve fiber growth and sprouting, to pain hypersensitivity has been investigated. Glial activation and inflammatory cytokines released by microglia and astrocytes are considered to be involved in the neural sprouting and plasticity. ⋯ Our results demonstrated that propentofylline could attenuate the CCI-induced mechanical allodynia and thermal hyperalgesia and inhibit the astrocyte activation and production of IL-1β. GAP-43 expression was also down-regulated by intrathecal propentofylline. These findings suggest that astrocyte activation is involved in the regulation of GAP-43 expression and propentofylline might be used in the treatment of neuropathic pain.
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Int J Clin Exp Patho · Jan 2013
IL4 and IL-17A provide a Th2/Th17-polarized inflammatory milieu in favor of TGF-β1 to induce bronchial epithelial-mesenchymal transition (EMT).
Severe asthma is a chronic airway disease characterized by the Th2/Th17-polarized inflammation along with permanent airway remodeling. Despite past extensive studies, the exact role for Th2 and Th17 cytokines in asthmatic pathoetiology, particularly in the pathogenesis of bronchial epithelial-mesenchymal transition (EMT), is yet to be fully addressed. We herein conducted studies in 16-HBE cells and demonstrated that Th2-derived IL-4 and Th17-derived IL-17A provide a chronic inflammatory milieu that favors TGF-β1 to induce bronchial EMT. ⋯ IL-4 and IL-17A synergized with TGF-β1 to induce epithelial cells re-entering cell cycle, and to promote epithelial to mesenchymal morphological transistion, and by which they enhanced the capacity of TGF-β1 to suppress E-cadherin expression, and to induce a-SMA expression in epithelial cells. Mechanistic studies revealed that this synergic action is coordinated by the regulation of ERK1/2 activity. Our results not only provide a novel insight into the understanding of the mechanisms underlying airway remodeling in asthmatic condition, but also have the potential for developing more effective therapeutic strategies against severe asthmatics in clinical settings.