Group IIA-soluble phospholipase A2 levels in patients with infections after esophageal cancer surgery.
ABSTRACT To examine the changes in blood-soluble phospholipase A(2)-IIA levels caused by surgical stress and postoperative infections.
We retrospectively analyzed a prospective database of 40 patients who underwent esophagectomy for esophageal cancer. Nine of these patients had a postoperative infection (E Inf(+) group), and 31 did not have a postoperative infection (E Inf(-) group). The blood sPLA(2)-IIA level was measured using a radioimmunoassay, and whole blood was stimulated with lipopolysaccharide (LPS) to examine the sPLA(2)-IIA production.
In the E Inf(-) group, the blood sPLA(2)-IIA levels peaked on postoperative day (POD) 3 then decreased gradually thereafter. Receiver-operator characteristic statistics based on the sPLA(2)-IIA values on POD 5, which are used to classify postoperative infectious complications, revealed an area under the curve of 0.789. However, stimulation of peripheral blood cells with LPS did not induce the production of sPLA(2)-IIA.
During the early postoperative phase, blood sPLA(2)-IIA levels increase according to the surgical stress. Soluble PLA(2)-IIA may be produced at the site of infection or in the liver, but not in the circulating blood. Sustained elevation of the serum sPLA(2)-IIA level, observed even after POD 3, seems to represent a response to postoperative infection.
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ABSTRACT: Bacteriophages have been used for more than a century for (unconventional) therapy of bacterial infections, for half a century as tools in genetic research, for 2 decades as tools for discovery of specific target-binding proteins, and for nearly a decade as tools for vaccination or as gene delivery vehicles. Here we present a novel application of filamentous bacteriophages (phages) as targeted drug carriers for the eradication of (pathogenic) bacteria. The phages are genetically modified to display a targeting moiety on their surface and are used to deliver a large payload of a cytotoxic drug to the target bacteria. The drug is linked to the phages by means of chemical conjugation through a labile linker subject to controlled release. In the conjugated state, the drug is in fact a prodrug devoid of cytotoxic activity and is activated following its dissociation from the phage at the target site in a temporally and spatially controlled manner. Our model target was Staphylococcus aureus, and the model drug was the antibiotic chloramphenicol. We demonstrated the potential of using filamentous phages as universal drug carriers for targetable cells involved in disease. Our approach replaces the selectivity of the drug itself with target selectivity borne by the targeting moiety, which may allow the reintroduction of nonspecific drugs that have thus far been excluded from antibacterial use (because of toxicity or low selectivity). Reintroduction of such drugs into the arsenal of useful tools may help to combat emerging bacterial antibiotic resistance.Antimicrobial Agents and Chemotherapy 07/2006; 50(6):2087-97. · 4.84 Impact Factor
Article: Plasma secretory phospholipase A2-IIa as a potential biomarker for lung cancer in patients with solitary pulmonary nodules.[show abstract] [hide abstract]
ABSTRACT: Five-year survival for lung cancer has remained at 16% over last several decades largely due to the fact that over 50% of patients are diagnosed with locally-advanced or metastatic disease. Diagnosis at an earlier and potentially curable stage is crucial. Solitary pulmonary nodules (SPNs) are common, but the difficulty lies in the determination of which SPN is malignant. Currently, there is no convenient and reliable biomarker effective for early diagnosis. Secretory phospholipase A2-IIa (sPLA2-IIa) is secreted into the circulation by cancer cells and may allow for an early detection of lung cancer. Plasma samples from healthy donors, patients with only benign SPN, and patients with lung cancer were analyzed. Expression of sPLA2-IIa protein in lung cancer tissues was also determined. We found that the levels of plasma sPLA2-IIa were significantly elevated in lung cancer patients. The receiver operating characteristic curve analysis, comparing lung cancer patients to patients with benign nodules, revealed an optimum cutoff value for plasma sPLA2-IIa of 2.4 ng/ml to predict an early stage cancer with 48% sensitivity and 86% specificity and up to 67% sensitivity for T2 stage lung cancer. Combined sPLA2-IIa, CEA, and Cyfra21.1 tests increased the sensitivity for lung cancer prediction. High level of plasma sPLA2-IIa was associated with a decreased overall cancer survival. sPLA2-IIa was overexpressed in almost all non-small cell lung cancer and in the majority of small cell lung cancer by immunohistochemistry analysis. Our finding strongly suggests that plasma sPLA2-IIa is a potential lung biomarker to distinguish benign nodules from lung cancer and to aid lung cancer diagnosis in patients with SPNs.BMC Cancer 12/2011; 11:513. · 3.01 Impact Factor