The aim of this study was to evaluate and compare the ability of C-11-methionine (MET) and F-18 fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) to diagnose lung cancer in patients with ...pneumoconiosis.
Twenty-six subjects underwent both whole-body MET-PET and FDG-PET on the same day. The first group was a lung cancer group, which consisted of 15 patients, and included those with pneumoconiosis with increased nodules (13 cases), hemoptysis (1 case), and positive sputum cytology (1 case). The second group was a no-malignancy control group, consisting of 11 patients with pneumoconiosis.
Significant correlations between nodule size and the maximum standardized uptake value (SUV(max)) of the two PET tracers were observed in the control group. The larger the nodule size, the greater were the amounts of these tracers accumulated (MET: r = 0.771, P < 0.0001; FDG: r = 0.903, P < 0.0001). The SUV(max) of MET was significantly lower than that of FDG in the pneumoconiotic nodules (P < 0.0001). Lung cancer was found in 5 of 19 nodules (two with adenocarcinoma, one with squamous cell carcinoma, one with small cell carcinoma, and one with large cell carcinoma) in the first group. As for nodules equal to or less than 3 cm in diameter, the SUV(max) of MET was significantly higher in the lung cancer than in the pneumoconiotic nodules, with 3.48 +/- 1.18 (mean +/- SE) for the lung cancer and 1.48 +/- 0.08 for the pneumoconiotic nodules (P < 0.01), similar to the SUV(max) of FDG, with 7.12 +/- 2.36 and 2.85 +/- 0.24 (P < 0.05), respectively. On the basis of the criteria for the control group, FDG and MET identified lung cancer with sensitivities of 60% and 80%, specificities of 100% and 93%, accuracies of 90% and 90%, positive predictive values of 100% and 80%, and negative predictive values of 88% and 93%, respectively.
Our results indicate that nodules with an intense uptake of MET and FDG relative to their size should be carefully observed because of a high risk for lung cancer.
Although it has been suspected that inflammation is associated with increased tumor metastasis, the exact type of immune response required to initiate cancer progression and metastasis remains ...unknown. In this study, by using an
in vivo
tumor progression model in which low tumorigenic cancer cells acquire malignant metastatic phenotype after exposure to inflammation, we found that
IL
‐17A is a critical cue for escalating cancer cell malignancy. We further demonstrated that the length of exposure to an inflammatory microenvironment could be associated with acquiring greater tumorigenicity and that
IL
‐17A was critical for amplifying such local inflammation, as observed in the production of
IL
‐1β and neutrophil infiltration following the cross‐talk between cancer and host stromal cells. We further determined that γδT cells expressing Vδ1 semi‐invariant
TCR
initiate cancer‐promoting inflammation by producing
IL
‐17A in an MyD88/
IL
‐23‐dependent manner. Finally, we identified
CD
30 as a key molecule in the inflammatory function of Vδ1T cells and the blockade of this pathway targeted this cancer immune‐escalation process. Collectively, these results reveal the importance of
IL
‐17A‐producing
CD
30
+
Vδ1T cells in triggering inflammation and orchestrating a microenvironment leading to cancer progression.
Salusin-β has been detected in numerous mammalian tissues and has been shown to have various effects on the cardiovascular system. In this study, we showed that salusin-β exhibited potent ...antibacterial activity against Gram-positive microorganisms such as Bacillus subtilis NBRC 3513, Bacillus megaterium ATCC 19213, Staphylococcus aureus NBRC 12732, and Staphylococcus epidermidis NBRC 12933. A cytoplasmic membrane-depolarizing assay using the DiSC3(5) dye revealed that the addition of 4 nmol/mL of salusin-β caused the leakage of fluorescence dye from Staphylococcus aureus NBRC 12732. The antimicrobial potency and circular dichroism (CD) spectroscopy of five analogs related to salusin-β were examined to determine structure-function relationships in its N- and C-terminal regions. The results obtained suggest that the N-terminal sequences of the salusin-β molecule are important for the expression of the potent antimicrobial activity of this peptide. A profile corresponding to that of the α-helix conformation was observed in the salusin-β solution.
The properties of ES46.5K, an esterase from mouse hepatic microsomes, were compared with those of carboxylesterases from rabbit and porcine liver. The inhibitory profile with a serine hydrolase ...inhibitor (bis-p-nitrophenylphosphate) and detergents (sodium dodecylsulfate, Emulgen 911) was different between ES46.5K and the carboxylesterases. Bis-p-nitrophenylphosphate (0.1 mM) markedly inhibited the catalytic activity of the carboxylesterases but not that of ES46.5K. Emulgen 911 (0.05—0.25%) inhibited the catalytic activity of the carboxylesterases, whereas the detergent conversely stimulated that of ES46.5K by 150%. The two carboxylesterases catalyzed the hydrolysis of acetate esters of tetrahydrocannabinol (THC) analogues with different side chain lengths (C1—C5), although ES46.5K showed marginal activity only against the acetate of Δ8-tetrahydrocannabiorcol, a methyl side chain derivative of Δ8-THC. ES46.5K hydrolyzed cannabinoid esters stereospecifically and regioselectively. The esterase hydrolyzed 8α-acetoxy-Δ9-tetrahydrocannabinol (8α-acetoxy-Δ9-THC, 5.62 nmol/min/mg protein), while the enzyme did not hydrolyze 8β-acetoxy-Δ9-THC, 7α-acetoxy-, and 7β-acetoxy-Δ8-THC at all. In contrast, the carboxylesterases from rabbit and porcine liver hydrolyzed 8β-acetoxy-Δ9-THC efficiently but not 8α-acetoxy-Δ9-THC. ES46.5K hydrolyzed side chain acetoxy derivatives of Δ8-THC at the 3′- and 4′-positions, and a methyl ester of 5′-nor-Δ8-THC-4′-oic acid. The enzyme, however, could not hydrolyze methyl esters of Δ8- and Δ9-THC-11-oic acid, while both carboxylesterases hydrolyzed side chain acetoxy derivatives of Δ8-THC and three methyl esters of THC-oic acids. These differences in stereospecificity and regioselectivity between ES46.5K and carboxylesterases suggest that the configurations of important amino acids for the catalytic activities of these enzymes are different from each other.
The TRK-fused gene (TFG in human, Tfg in rat) was originally identified in human papillary thyroid cancer as a chimeric form of the NTRK1 gene. It has been reported that the gene product (TFG) plays ...a role in regulating phosphotyrosine-specific phosphatase-1 activity. However, no information regarding the localization of Tfg in rat tissues is available. In this study, we investigated the expression of Tfg mRNA in normal rat tissues using reverse transcription-polymerase chain reaction (RT-PCR). We also produced an antibody against Tfg gene products and examined the localization of TFG in the rat brain and retina. The RT-PCR experiments demonstrated that two types of Tfg mRNA were expressed in rat tissues: the conventional form of Tfg (cTfg) and a novel variant form, retinal Tfg (rTfg). RT-PCR analyses demonstrated that cTfg was ubiquitously expressed in rat tissues, while rTfg was predominantly expressed in the brain and retina. Western blot analysis demonstrated two bands with molecular weights of about 30 kDa and 50 kDa in the rat brain. Immunohistochemistry indicated that TFG proteins were predominantly expressed by neurons in the brain. In the rat retina, intense TFG-immunoreactivity was detected in the layer of rods and cones and the outer plexiform layer.
Clinical studies suggest a role for angiogenesis in the development and persistence of chronic asthma, but whether angiogenic mediators contribute to acute asthma has not been fully studied.
The aim ...of this study was to investigate a role of vascular endothelial growth factor (VEGF), a major angiogenic and proinflammatory mediator, in allergen-induced acute asthma and to determine whether endostatin/Fc, a potent antiangiogenic factor can attenuate allergic airway responses.
We sensitized BALB/c mice with ovalbumin. We measured serum VEGF and examined immunoreactive VEGF around the airways 48 hours after the last challenge with either aerosolized PBS or ovalbumin once per day for 3 days. We also treated ovalbumin-sensitized mice with either endostatin/Fc or control fusion protein at the time of challenge with ovalbumin. We analyzed allergic airway responses 48 hours after the last ovalbumin challenge.
Ovalbumin challenge induced immunolocalization of numerous VEGF-positive cells around airways and increased serum VEGF levels. Treatment with endostatin/Fc inhibited the airway hyperresponsiveness, pulmonary allergic inflammation, production of ovalbumin-specific IgE, and lung inflammatory mediators. Both VEGF-dependent and independent mechanisms are indicated by results using antibody blockade of VEGF receptors, which caused decreased allergic pulmonary inflammation but did not alter airway hyperresponsiveness or serum IgE levels.
These data demonstrate for the first time that recombinant endostatin can prevent the development of asthma features in a mouse model and suggest that this class of agents merits further study as novel therapeutics for asthma.
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