The inhibitory effect of recombinant human Cu++Zn++superoxide dismutase (rhSOD) on metastasis of tumor cells in the mouse was investigated. In an experimental pulmonary metastasis model employing Meth A cells as inoculum, significant inhibition of metastasis was obtained by intravenous pre- and post-administration of rhSOD. An inhibitory effect of rhSOD was also observed in a spontaneous pulmonary metastasis model with 3LL cells as the inoculum. rhSOD was not observed to have any significant effects on the platelet-aggregating activity of tumor cells, the adhesiveness of tumor cells to vascular components (endothelial cells, laminin and type-IV collagen), or the growth of tumor cells either in vitro or in vivo. However, rhSOD suppressed invasion of Meth A and 3LL cells into Matrigel (an artificially reconstituted basement membrane of collagen, laminin and heparan sulfate) in the presence of hypoxanthine and xanthine oxidase, in vitro producers of superoxide. Thus, the present study shows that rhSOD is able to inhibit both experimental and spontaneous pulmonary metastasis, possibly through the suppression of tumor cell invasion into the extracellular matrix.
We have previously described an inverse relationship between Cu-Zn superoxide dismutase (SOD) activity and invasiveness of a clone of human tongue cancer cells. In these cells, suppression of Cu-Zn SOD activity by transfection with anti-sense cDNA enhanced motility in vitro. The present studies were undertaken to determine whether the inverse relationship between intracellular Cu-Zn SOD activity and motility is a general property of other tumor cells and whether this enzyme indeed defines in vivo metastatic potential. Murine Meth A sarcoma-derived ML-01 cells, which have low metastatic activity, were transfected with anti-sense Cu-Zn SOD cDNA. Two clones with very different SOD activities-ML-AS2, with the most suppressed, and ML-AS5, with the least suppressed activity-were analyzed for their motility and metastatic capability. Compared to the mocktransfectant ML-neo, the metastatic potential and motility of the ML-AS2 and ML-AS5 were increased 4.5-and 2.1-fold, respectively. Superoxide treatment enhanced the motility of the AS clones but not that of the ML-neo cells. Our results clearly show that there is an inverse relationship between the intracellular level of Cu-Zn SOD, cell motility and in vivo metastatic potential. Int.
We have previously reported that superoxide stimulates the motility of tumor cells and the administration of Cu-Zn superoxide dismutase (SOD) significantly suppresses metastasis. However, ideally, anti-metastatic therapy should be longlasting, systemically effective and have low toxicity. The halflife of Cu-Zn SOD in plasma is so short that it cannot provide long-lasting effects. Therefore, in this study we have developed a gene therapy in a mouse model utilizing extracellular SOD (EC-SOD), which is the most prevalent SOD
Background/ObjectivesThis historical control study examined the differences in the incidence of postoperative pneumonia between patients administered liquid and semi-solid nutrients after percutaneous endoscopic gastrostomy (PEG).Subjects/MethodsThe medical records of adult patients who underwent PEG between March 1999 and March 2014 were investigated. The patients were administered either liquid or semi-solid nutrient and examined for gastroesophageal reflux via radiography after PEG. The study period was divided into periods I (liquid nutrient to all patients), II (semi-solid nutrient to patients with reflux and liquid nutrient to those without), and III (semi-solid nutrient to all patients). The patient characteristics and incidence of postoperative pneumonia were stratified by the periods. To assess the relationship between postoperative pneumonia and the periods, a logistic regression analysis was performed.ResultsOf 370 patients enrolled, 149 were in period I, 64 in period II, and 157 in period III. Postoperative pneumonia was more frequently observed in period I (20.8%) than in periods II (7.8%) and III (10.2%). The odds ratios were higher in period I (period I vs. II: 3.10 [95% confidence intervals: 1.15–8.38]; period I vs. III: 2.32 [1.21–4.44]). The incidence of gastroesophageal reflux did not greatly differ between periods II (25.0%) and III (35.0%).ConclusionsThe incidence of postoperative pneumonia after PEG was lower in the patients administered semi-solid nutrient than in those administered liquid nutrient, suggesting that semi-solid nutrient administration to patients with PEG tubes is preferable to prevent postoperative pneumonia. Furthermore, it may be favored especially in those with gastroesophageal reflux.
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