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Biomedical subjects

I Lee

Publications and source records attributed to I Lee.

257 records · Page 15Linked to original sources

Enhanced cellular radiation sensitivity of androgen-independent human prostate tumor cells by onconase.

The RNase-like onconase, isolated from amphibian oocytes, showed increases in median tumor pO2 in solid tumors (1). This led us to consider if onconase could decrease cellular O2 consumption (QO2) on 9L rat glioma as well as DU145 human prostate adenocarcinoma cells. Using a Clark-type electrode chamber, we observed that onconase significantly inhibited QO2 in both tumors we tested. Since onconase-induced reduction in QO2 could lead to increases in radiation sensitivity, due to the diffusion of O2 to previously hypoxic tumor cells, we used androgen-insensitive DU145 cells to study onconase-induced changes in radiation sensitivity in vitro. Radiation sensitization was achieved with > 5 micrograms/ml of onconase, regardless of the p53 status of tumor cells. Data presented here suggested that onconase-induced enhancement in radiation sensitization in vitro of androgen-insensitive prostate cancer cells warranted further studies of radiation responses in vivo, prior to clinical settings for the advanced-stages of prostate cancer.

Adenocarcinoma↗

Physiological mechanisms of radiation sensitization by pentoxifylline.

The aim of this study was to investigate whether multiple injections (daily for 5 days) of the hemorheological agent pentoxifylline (PTX) affected tumor physiological parameters (i.e., tumor pO2, tumor pH, and tumor interstitial fluid pressure) during the tumor growth of FSaII murine fibrosarcoma in C3H mice. The radiation sensitization by multiple injections of PTX (daily for 5 days) was also studied. Following multiple administrations of PTX, PTX significantly improved tumor oxygenation in all sizes of tumors tested. Our results showed that the elevated tumor interstitial fluid pressure (TIFP) in solid tumors could be reduced by PTX. Based on our results with the improvement in tumor pathophysiology, PTX may be of use during tumor therapies in which the outcome may be detrimentally affected by the presence of hypoxia. As anticipated, multiple injections of PTX with fractionated x-irradiation prolonged the radiation-induced growth delay in FSaII tumors, producing an enhancement ratio of 1.8 of the growth delay at 15 days. However, we did not observe any alteration in cellular oxygen consumption (QO2) after the treatment with PTX. Therefore, we concluded that PTX-induced radiosensitization was due to an increase in tumor pO2, not a reduction in QO2.

Animals↗

Ursolic acid-induced changes in tumor growth, O2 consumption, and tumor interstitial fluid pressure.

The anti-tumor effect of ursolic acid (UA) and UA-induced changes in tumor physiology in tumor-bearing mice were examined. MTT colorimetric assay, clonogenic assay, and growth-delay assay for the determination of tumoricidal effects of UA were evaluated. UA-induced apoptosis was measured by fluorescent microscopy, stained by propidium iodide. Oxygen consumption (QO2) after treatment with UA was measured using a Clark-type electrode chamber. Systemic toxicity in mice was assayed by LD50(30). We also measured UA-induced changes in several tumor physiological parameters. Inhibitory effect of UA on various tumor cell lines was observed using MTT and clonogenic assays in vitro. UA-induced apoptosis significantly increased in a dose-dependent manner. Cellular QO2 values were significantly reduced by UA. In animal studies, UA significantly reduced tumor interstitial fluid pressure (TIFP) to approximately 40% of the control values at 2-3 days post-treatment (P<0.05). An i.p. administration of 100 mg/kg of UA significantly (P<0.01) inhibited tumor growth of FSaII. In conclusion, UA showed anti-tumor effect on various tumor cells in vitro as well as a moderate retardation of growth in two tumor models in vivo. We gained some insight regarding the pathophysiological benefits of UA (i.e., reduction in TIFP) as a cancer therapeutic agent. Consequently, these observations can be used for further study of UA or to facilitate clinical applications of UA for treating cancer patients.

Animals↗

Comparison of xylazine, lidocaine and the two drugs combined for modified dorsolumbar epidural anaesthesia in cattle.

Twenty-four Holstein cattle scheduled for flank surgery in a standing position were randomly assigned to four groups of six. A 16 G, 120 mm Tuohy needle was inserted into the first interlumbar epidural space and its position was confirmed by the hanging drop technique. After air had been allowed to enter freely for approximately one minute, the epidural needle was slowly inserted 7 to 10 mm deeper to penetrate the epidural fat, and anaesthetic solution containing either 0.05 mg/kg bodyweight xylazine hydrochloride (xylazine), 0.025 mg/kg xylazine, 0.025 mg/kg xylazine and 0.1 mg/kg lidocaine hydrochloride (lidocaine), or 0.2 mg/kg lidocaine alone was administered. Signs of sedation were observed in the three groups treated with xylazine and the number of spinal segments involved in the area of analgesia when the anaesthetic contained xylazine was significantly greater than with 0.2 mg/kg lidocaine alone ( < 0.01). After the treatment with 0-025 mg/kg xylazine and 0.1 mg/kg lidocaine, flank surgery was performed successfully without additional line block or side effects.

Adrenergic alpha-Agonists↗

The fluid dynamic effect on protein adsorption in left ventricular assist devices.

Plasma protein adsorption onto an artificial surface is strongly influenced by not only the surface characteristics of materials, but also by the fluid dynamics inside the blood pump, and it would influence subsequent platelet adhesion or activation, which plays a major role in the initiation of thrombus formation at the blood-material interface in vivo. In vitro flow visualization of an electrohydraulic LVAD was performed by a video camera (CCD, Hitachi) and an image processor (PC VISION PLUS) with an IBM PC. The electrohydraulic LVADs were implanted in mongrel dogs of approximately 20 kg. The authors sectioned the blood contacted ventricle after animal death according to the level of shear rate. Because analysis of adsorbed protein might be influenced by the size of the ventricle segment, the number of segments was limited to eight per ventricle. Platelet adhesion and its morphology were observed by scanning electron microscopy (SEM). Adsorbed plasma proteins (fibrinogen, albumin, and IgG) on each segment were quantified by enzyme linked immunosorbent assay (ELISA). The specimens were soaked in 2% (wt/vol) SDS/PBS for 2 days and the released protein concentration assessed. A well developed large vortex was observed at the center of the artificial ventricle. Polyurethane blood pumps displayed different degrees of protein adsorption and subsequent platelet adhesion on each segment.

Adsorption↗