ABSTRACT
BACKGROUND: Despite major advances in lung cancer treatment, early detection remains the most promising way of improving outcomes. To detect lung cancer in earlier stages, many serum biomarkers have been tested. Unfortunately, no single biomarker can reliably detect lung cancer. We combined a set of 2 tumor markers and 4 inflammatory or metabolic markers and tried to validate the diagnostic performance in lung cancer. METHODS: We collected serum samples from 355 lung cancer patients and 590 control subjects and divided them into training and validation datasets. After measuring serum levels of 6 biomarkers (human epididymis secretory protein 4 [HE4], carcinoembryonic antigen [CEA], regulated on activation, normal T cell expressed and secreted [RANTES], apolipoprotein A2 [ApoA2], transthyretin [TTR], and secretory vascular cell adhesion molecule-1 [sVCAM-1]), we tested various sets of biomarkers for their diagnostic performance in lung cancer. RESULTS: In a training dataset, the area under the curve (AUC) values were 0.821 for HE4, 0.753 for CEA, 0.858 for RANTES, 0.867 for ApoA2, 0.830 for TTR, and 0.552 for sVCAM-1. A model using all 6 biomarkers and age yielded an AUC value of 0.986 and sensitivity of 93.2% (cutoff at specificity 94%). Applying this model to the validation dataset showed similar results. The AUC value of the model was 0.988, with sensitivity of 93.33% and specificity of 92.00% at the same cutoff point used in the validation dataset. Analyses by stages and histologic subtypes all yielded similar results. CONCLUSIONS: Combining multiple tumor and systemic inflammatory markers proved to be a valid strategy in the diagnosis of lung cancer.
Subject(s)
Humans , Male , Apolipoprotein A-II , Area Under Curve , Biomarkers , Biomarkers, Tumor , Carcinoembryonic Antigen , Chemokine CCL5 , Dataset , Diagnosis , Epididymis , Lung Neoplasms , Lung , Prealbumin , Sensitivity and Specificity , Vascular Cell Adhesion Molecule-1ABSTRACT
In Table 2 and 3, cutoff values of RANTES, ApoA2, TTR, Svcam-1 (and sensitivity and specificity values accordingly) were wrongly marked.
ABSTRACT
Inadvertent application of ionizing radiation, a valuable tool in diagnostic radiology and radiotherapy, results in injury and death of adjacent normal cells, inducing gene mutations or even producing latent cancers. Captopril, an angiotensin I converting enzyme (ACE) inhibitor, has been reported to prevent the structural and functional changes in variable organs, such as lung and kidney, from radiation injury in different experimental animal models. An experiment was carried out to elucidate the radiation-induced histomorphologic changes of small intestine, especially jejunum, and to determine whether captopril can reduce or prevent the radiation-induced injuries in jejunum. Twenty-six healthy Sprague-Dawley rats were used. Experimental group (n=24) was divided into two large groups: the first one (n=16) was treated with two different single dose (9 Gy, 17 Gy) irradiation only and was sacrificed at 12 hours and at 8 weeks following irradiation; the second one (n=8) received captopril 500 mg/l per oral continuously after same doses of irradiation and was sacrificed at 8 weeks. The control group (n=2) was maintained on a stock diet in a same period of experimental group and sacrificed coincidentally. On light and electron microscopy, the 9 Gy and 17 Gy 12 hours groups revealed frequent apoptosis and necrosis but extremely decreased mitotic figures of the crypt cells. However, the 9 Gy and 17 Gy 8 weeks groups and the combined irradiation with captopril groups showed extremely reduced apoptosis and necrosis with increased mitotic figures. There was good correlation between experimental groups in apoptotic count and mitotic count (p<0.05). In the 9 Gy and 17 Gy 12 hours groups, the mucosal surface was focally or diffusely fragmented and the villi were slightly to moderately distorted. Collagen deposition was very mild and confined to the lower portion of the lamina propria. The 9 Gy and 17 Gy 8 weeks groups showed more severe mucosal surface fragmentation even with foci of erosion, short and distorted villi, and more intense collagen deposition. In contrast, the combined irradiation with captopril groups revealed complete regeneration of the mucosal surface epithelium and absent collagen deposition. These findings suggest that the acute radiation injuries to small intestine occur principally in the mucosal crypt cells. Captopril, the ACE inhibitor, might provide a useful intervention in the radiation injuries of intestinal mucosa.
Subject(s)
Animals , Rats , Apoptosis , Captopril , Collagen , Diet , Epithelium , Intestinal Mucosa , Intestine, Small , Jejunum , Kidney , Lung , Microscopy, Electron , Models, Animal , Mucous Membrane , Necrosis , Peptidyl-Dipeptidase A , Radiation Injuries , Radiation, Ionizing , Radiotherapy , Rats, Sprague-Dawley , RegenerationABSTRACT
Seven fibrovascular diabetic preretinal membranes were examined with lightmicroscophic immunohistochemical stain and electron-microscopy to evaluate the possibility of pericytes to be involved in membrane contraction. Pericytes were positively stained with anti-actin antibody together with some stromal cells thought to be myofibroblasts presumedly. On transmission electron microscopic study, pericytes were highly active with numerous cytoplasmic processes and contained abundant microfilaments considered as actin in their cytoplasm. Pericyte/endothelial cell ratio of vascular channels were increased in some actively proliferative portion of the membranes. Myofibroblasts that contain abundant cytoplasmic microfilaments were also demonstrated in the extravascular stroma of the membranes and were very similar to the pericytes morphologically. Although the evidence that the pericytes are related to the origin of the myofibroblasts could not be demonstrated, this study suggested that the pericytes may play important roles in development and contraction mechanism of fibrovascular diabetic preretinal membranes.