Malathion carboxylesterase titer and its relationship to malathion toxicity

The titer of malathion carboxylesterase in liver and sera of rats, three strains of mice, and five groups of pretreated mice was correlated with the malathion LD50 values measured in these groups. The equation of a regression line relating enzyme titer to toxicity was used to predict the median lethal dosage of purified malathion to humans. The mean value, 3655 mg/kg, was compared with dosages ingested in actual cases of human malathion poisonings. A discrepancy was noted between the LD50 value predicted in this study and the life-threatening doses of commercial malathion reported in the clinical literature. The unexpectedly high toxicity of commercial malathion may be related to its content of esterase-inactivating impurities.     

Use of a radioimmunoassay to quantify thrombospondin

Results of radioimmunoassay procedures applied to samples containing thrombospondin indicated that reliable values are obtained either in saline or in plasma. Plasma levels in apparently normal individuals ranged from approximately 20 to 300 ng/ml. The mean for 20 individuals was 175 ng/ml. Plasma specimens stored either refrigerated at 4 degrees C or frozen at -80 degrees C showed significantly diminished thrombospondin levels over a period of 90 days. Serum levels of thrombospondin were found to range from 10,000 to 30,000 ng/ml.     

Pneumothorax: appearance on lateral chest radiographs

The appearance of pneumothorax on lateral radiographs obtained with the patient erect were reviewed in 100 patients (122 total examinations). A pneumothorax could be seen on the lateral projection in 89% of the examinations (109 of 122). The displaced pleural line was most frequently identified anteriorly or posteriorly and was less commonly identified at the lung apex or in a subpulmonic location. In 11 cases, an air-fluid level was the only recognizable finding of a pneumothorax on the lateral projection. Although in 27% of examinations (32 of 122) the pneumothorax was either not seen (11%) (n = 13) or was a subtle finding (16%) (n = 19), in 14% of examinations (17 of 122) the lateral projection provided helpful information to supplement the posteroanterior projection.     

Identification of oligopeptides binding to peritoneal tumors of gastric cancer

This is a report of in vivo intraperitoneal biopanning, and we successfully identified a novel peptide to target the multiple peritoneal tumors of gastric cancer. A phage display library was injected directly into the abdominal cavity of mice bearing peritoneal tumors of human gastric cancer, and phages associated with the tumors were subsequently reclaimed from isolated samples. The tumor-associated phages were amplified and the biopanning cycle was repeated five times to enrich for high affinity tumor-selective binding peptides. Finally, a tri-peptide motif, KLP, which showed homology with laminin 5 (a ligand for alpha3beta1 integrin), was identified as a binding peptide for peritoneal tumors of gastric cancer. Phage clones displaying the sequence KLP showed 64-fold higher binding to peritoneal tumors than control phage and were preferentially distributed in tumors rather than in normal organs after intraperitoneal injection into mice. In addition, the KLP phages were more likely to bind to cancer cells in malignant ascites derived from a patient with recurrent gastric cancer. Synthesized peptide containing the motif KLP (SWKLPPS) also showed a strong binding activity to peritoneal tumors without cancer growth effect. Liposomes conjugated with SWKLPPS peptide appeared significantly more often in tumors than control liposomes after intraperitoneal injection into mice. Furthermore, modification of liposomes with SWKLPPS peptide enhanced the antitumor activity of adriamycin on gastric cancer cells. The peptide motif KLP seems a potential targeting ligand for the treatment of peritoneal metastasis of gastric cancer.     

Identification of an oligopeptide binding to hepatocellular carcinoma

OBJECTIVES: We carried out identification of a small peptide binding to human hepatocellular carcinoma (HCC) cells with the aim of applying the peptide for future HCC-targeted therapy or imaging. METHODS: The biopanning technique using phage peptide display libraries was performed on HCC cells in vitro, and a phage clone expressing the HCC-binding peptide motif was selected. The binding activity of the selected phage was evaluated by plaque infection assay and immunofluorescence on cell lines. In addition, the binding activity of the peptide-expressing phage was investigated using HCC specimens derived from patients who had undergone hepatectomy for HCC. RESULTS: A heptapetide, Thr-Thr-Pro-Arg-Asp-Ala-Tyr (TTPRDAY), was identified as a motif binding to HCC. TTPRDAY bound specifically to HCC cells in comparison with other cancer cells, and the binding to HCC cells was also confirmed by immunofluorescence. In addition, the synthesized TTPRDAY peptide showed binding activity and a non-mitogenic effect on HCC cells in vitro. TTPRDAY-presenting phage showed more significant binding to HCC cells derived from specimens obtained from actual patients than to non-cancerous liver tissue. CONCLUSION: The motif TTPRDAY, identified by the biopanning technique, shows significant binding to HCC cells.