Purpose: One of the main challenges of lung cancer research is identifying patients at high risk for recurrence after surgical resection. Simple, accurate, and reproducible methods of evaluating individual risks of recurrence are needed. Experimental Design: Based on a combined analysis of time-to-recurrence data, censoring information, and microarray data from a set of 138 patients, we selected statistically significant genes thought to be predictive of disease recurrence. The number of genes was further reduced by eliminating those whose expression levels were not reproducible by real-time quantitative PCR. Within these variables, a recurrence prediction model was constructed using Cox proportional hazard regression and validated via two independent cohorts (n = 56 and n = 59). Results: After performing a log-rank test of the microarray data and successively selecting genes based on real-time quantitative PCR analysis, the most significant 18 genes had P values of <0.05.After subsequent stepwise variable selection based on gene expression information and clinical variables, the recurrence prediction model consisted of six genes (CALB1, MMP7, SLC1A7, GSTA1, CCL19, and IFI44). Two pathologic variables, pStage and cellular differentiation, were developed. Validation by two independent cohorts confirmed that the proposed model is significantly accurate (P = 0.0314 and 0.0305, respectively). The predicted median recurrence-free survival times for each patient correlated well with the actual data. Conclusions: We have developed an accurate, technically simple, and reproducible method for predicting individual recurrence risks. This model would potentially be useful in developing customized strategies for managing lung cancer.
After spinal cord injury, the disruption of blood-spinal cord barrier by activation of matrix metalloprotease is a critical event leading to infiltration of blood cells, inflammatory responses and neuronal cell death, contributing to permanent neurological disability. Recent evidence indicates that fluoxetine, an anti-depressant drug, is shown to have neuroprotective effects in ischaemic brain injury, but the precise mechanism underlying its protective effects is largely unknown. Here, we show that fluoxetine prevented blood-spinal cord barrier disruption via inhibition of matrix metalloprotease activation after spinal cord injury. After a moderate contusion injury at the T9 level of spinal cord with an infinite horizon impactor in the mouse, fluoxetine (10 mg/kg) was injected intraperitoneally and further administered once a day for indicated time points. Fluoxetine treatment significantly inhibited messenger RNA expression of matrix metalloprotease 2, 9 and 12 after spinal cord injury. By zymography and fluorimetric enzyme activity assay, fluoxetine also significantly reduced matrix metalloprotease 2 and matrix metalloprotease 9 activities after injury. In addition, fluoxetine inhibited nuclear factor kappa B-dependent matrix metalloprotease 9 expression in bEnd.3, a brain endothelial cell line, after oxygen-glucose deprivation/reoxygenation. Fluoxetine also attenuated the loss of tight junction molecules such as zona occludens 1 and occludin after injury in vivo as well as in bEnd.3 cultures. By immunofluorescence staining, fluoxetine prevented the breakdown of the tight junction integrity in endothelial cells of blood vessel after injury. Furthermore, fluoxetine inhibited the messenger RNA expression of chemokines such as Groα, MIP1α and 1β, and prevented the infiltration of neutrophils and macrophages, and reduced the expression of inflammatory mediators after injury. Finally, fluoxetine attenuated apoptotic cell death and improved locomotor function after injury. Thus, our results indicate that fluoxetine improved functional recovery in part by inhibiting matrix metalloprotease activation and preventing blood-spinal cord barrier disruption after spinal cord injury. Furthermore, our study suggests that fluoxetine may represent a potential therapeutic agent for preserving blood-brain barrier integrity following ischaemic brain injury and spinal cord injury in humans.
Combined use of US elastography and color Doppler US increases both the accuracy in distinguishing benign from malignant masses and the specificity in decision-making for biopsy recommendation at B-mode US.
The blood-brain barrier (BBB) including blood-spinal cord barrier (BSCB) is a highly specialized brain endothelial structure of the fully differentiated neurovascular system. When damaged by various insults including traumatic spinal cord injury (SCI), the BBB or BSCB disruption elicits blood infiltration and inflammation, thereby generating neurotoxic products that can compromise synaptic and neuronal functions (Hawkins and Davis 2005;Zlokovic 2005;Abbott et al. 2006) and induces the ''programmed death'' of neurons and glia, leading to permanent neurological deficits (Xu et al. 2001;Noble et al. 2002;Gerzanich et al. 2009 Seoul, KoreaAbstract The disruption of blood-spinal cord barrier (BSCB) after spinal cord injury (SCI) elicits an intensive local inflammation by the infiltration of blood cells such as neutrophils and macrophages, leading to cell death and permanent neurological disability. SCI activates matrix metalloprotease-9 (MMP-9), which is known to induce BSCB disruption. Here, we examined whether valproic acid (VPA), a histone deacetylase inhibitor, would attenuate BSCB disruption by inhibiting MMP-9 activity, leading to improvement of functional outcome after SCI. After moderate spinal cord contusion injury at T9, VPA (300 mg/kg) were immediately injected subcutaneously and further injected every 12 h for 5 days. Our data show that VPA inhibited MMP-9 activity after injury, and attenuated BSCB permeability and degradation of tight junction molecules such as occludin and ZO-1. In addition, VPA reduced the expression of inflammatory mediators including tumor necrosis factor-a. Furthermore, VPA increased the levels of acetylated histone 3, pAkt, and heat-shock protein 27 and 70, which have antiapoptotic functions after SCI. Finally, VPA inhibited apoptotic cell death and caspase 3 activation, reduced the lesion volume and improved functional recovery after injury. Thus, our results demonstrated that VPA improves functional recovery by attenuating BSCB disruption via inhibition of MMP-9 activity after SCI.
Color (power) Doppler imaging is a valuable adjunct to conventional sonography in differentiating between malignant and benign breast lesions.
15, a triblock polymer (Pluronic P123, EO 20 PO 70 EO 20 , M av = 5800, Aldrich) was used as the structure-directing agent and tetraethoxysilicate (TEOS) as the silica source [11]. Three SBA-15 samples were prepared from hydrothermal synthesis at 40, 100, and 130 C [11]. The calcined SBA-15 samples were then used as templates for the preparation of three mesoporous carbon (CMK-3) samples [12]. Sucrose was used as the carbon source with a pyrolysis ramp rate of 5 C min ±1 and a final pyrolysis temperature of 900 C. The silica was then removed using hydrofluoric acid and the resulting CMK-3 samples dried at 150 C. The mesoporous carbons were designated as CMK-3A, CMK-3B, and CMK3-C for samples templated by SBA-15 synthesized at 40, 100, and 130 C, respectively. The three CMK-3 samples were then used as template for the synthesis of mesoporous ZSM-5 as follows [7]: CMK-3 was impregnated to incipient wetness with a solution containing tetrapropylammonium hydroxide (TPAOH), aluminum isopropoxide [Al(OC 3 H 7 ) 3 ], water, and ethanol. Following the slow evaporation of ethanol from the mixture at room temperature, TEOS was added to the mixture at a C/SiO 2 ratio of 2:1 (w/w) to give a molar composition of the impregnated synthesis gel of TEOS: Al(OC 3 H 7 ) 3 / TPAOH/H 2 O/NaOH 0.02:0.36:16.2:0.006. The resulting mixture was heated in an autoclave at 180 C for 48 h to allow for crystallization of the ZSM-5 zeolite. The resulting powder was calcined in air at 550 C for 8 h to remove the CMK-3 template and organic additives. The mesoporous ZSM-5 zeolites were designated as MZSM-5A, MZSM-5B, and MZSM-5C for samples templated by CMK-3A, CMK-3B, and CMK-3C, respectively. A conventional ZSM-5 sample was also synthesized as described above but without the use of CMK-3.Characterization: Powder XRD analysis was performed using a Philips 1830 powder diffractometer with Cu Ka radiation (40 kV, 40 mA). Nitrogen sorption isotherms and textural properties of the materials were determined at ±196 C using nitrogen in a conventional volumetric technique by a Coulter SA3100 sorptometer. Before analysis the samples were oven dried at 150 C and evacuated for 12 h at 200 C under vacuum. The surface area was calculated using the Brunauer±Emmett±Teller (BET) method based on adsorption data in the partial pressure (P/P 0 ) range 0.05±0.2 and total pore volume was determined from the amount of the nitrogen adsorbed at P/P 0 = ca. 0.99. Micropore surface area and micropore volume were obtained via t-plot analysis. Scanning electron microscopy (SEM) images were recorded using a JEOL JSM-820 scanning electron microscope. Samples were mounted using a conductive carbon double-sided sticky tape. A thin (ca. 10 nm) coating of gold sputter was deposited onto the samples to reduce the effects of charging. Transmission electron microscopy (TEM) images were recorded on a JEOL 2000-FX electron microscope operating at 200 kV. Samples for analysis were prepared by spreading them on a holey carbon film supported on a grid. Thermogravimetric analysis of the a...
Identification of molecular markers often leads to important clinical applications such as early diagnosis, prognosis, and drug targeting. Lung cancer, the leading cause of cancerrelated deaths, still lacks reliable molecular markers. We have combined the bioinformatics analysis of the public gene expression data and clinical validation to identify biomarker genes for non-small-cell lung cancer. The serial analysis of gene expression and the expressed sequence tag data were meta
Ultrasound (US) elastography is a valuable imaging technique for tissue characterization. Two main types of elastography, strain and shear-wave, are commonly used to image breast tissue. The use of elastography is expected to increase, particularly with the increased use of US for breast screening. Recently, the US elastographic features of breast masses have been incorporated into the 2nd edition of the Breast Imaging Reporting and Data System (BI-RADS) US lexicon as associated findings. This review suggests practical guidelines for breast US elastography in consensus with the Korean Breast Elastography Study Group, which was formed in August 2013 to perform a multicenter prospective study on the use of elastography for US breast screening. This article is focused on the role of elastography in combination with B-mode US for the evaluation of breast masses. Practical tips for adequate data acquisition and the interpretation of elastography results are also presented.
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