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J Y Guan

Publications and source records attributed to J Y Guan.

7 recordsLinked to original sources
PubMed2001

Cross-resistance and combined cytotoxic effects of paclitaxel and cisplatin in bladder cancer cells.

PURPOSE: We studied the cross-resistance and combined cytotoxic effects of cisplatin and paclitaxel in bladder cancer cells in vitro. MATERIALS AND METHODS: The cytotoxicity of the 2 agents alone or in combination were studied in the bladder cancer cell line NTUB1 and the 2 sublines NTUB1/P, which is cisplatin resistant, and NTUB1/T, which is paclitaxel resistant, using the microculture tetrazolium assay. Schedule dependence of the 2-drug combination was assayed using 3 treatment schedules, including 1 concurrent and 2 sequential exposures. RESULTS: The mean cisplatin concentration plus or minus standard error of the means inhibiting 50% of the growth of NTUB1, NTUB1/P and NTUB1/T was 1.9 +/- 0.19, 19.3 +/- 2.33 and 2.1 +/- 0.15 microM., respectively, and the mean paclitaxel concentration inhibiting 50% of the growth of the 3 cell lines was 30 +/- 3.9, 1,033 +/- 120 and 110 +/- 15 nM., respectively. NTUB1/P had strong cross-resistance to paclitaxel. In contrast, NTUB1/T was as sensitive as NTUB1 to cisplatin. On median effect analysis the combined effects of the 2 agents given concurrently were sub-additive in the low fraction affected range of 0.1 to 0.3 and additive in the median to high fraction affected range of 0.4 to 1.0 in the 3 cell lines. Combined cytotoxicity was more synergistic when paclitaxel was given 24 hours earlier than cisplatin. The effects were less synergistic when cisplatin was given before paclitaxel. This phenomenon was noted in sensitive and resistant cells. CONCLUSIONS: In our bladder cancer cell model cisplatin resistant cells have strong cross-resistance to paclitaxel, whereas paclitaxel resistant cells are sensitive to cisplatin. The combined effects may be optimized by sequential use of the 2 agents, preferably paclitaxel given 24 hours before cisplatin. Our results have clinical implications for the treatment of bladder cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Megestrol acetate antagonizes cisplatin cytotoxicity.

Megestrol acetate (MGA) is being widely used for the improvement of appetite and performance status in patients receiving chemotherapy, especially cisplatin-containing therapy. However, little is known about whether MGA has an effect on cisplatin cytotoxicity. We have investigated this using two transitional carcinoma cell lines, i.e. the cisplatin-sensitive parental line NTUB1 and the resistant daughter line NTUB1/P. Combined effects of MGA and cisplatin were assayed with a microculture chemosensitivity method. We explored the level changes of several cisplatin detoxification mechanisms, including metallothionein (MT), glutathione S-transferase-pi (GST-pi) and glutathione (GSH) levels in cells treated with or without MGA. After treatment with 10 microns MGA for 24 h, the cisplatin IC50s of NTUB1 and NTUB1/P increased 1.4- (p = 0.03) and 1.6- (p = 0.02) fold, respectively. By median effect analysis, the combinations of MGA and cisplatin in the two cells appeared to produce an antagonistic interaction. By Northern analysis, MT transcript levels in both cells were significantly upregulated after treatment with MGA, as compared to those without treatment. Exposure to MGA in either sensitive or resistant cells did not alter GST-pi levels as shown by immunoblotting analysis. Cellular GSH content was increased only in NTUB1/P (p = 0.0036) but remained unchanged in NTUB1 cells (p = 0.29) after MGA exposure. In conclusion, MGA may antagonize cisplatin cytotoxicity by upregulating cellular MT and GSH levels. Use of MGA in cisplatin-containing chemotherapy may impair tumor response by antagonizing cisplatin antitumor activity.

Antineoplastic Agents↗
PubMed1995

Difference in effects of classic and phospholipid hydroperoxide glutathione peroxidases on liver lipid peroxide level in selenium-deficient rats.

When weanling male rats of the Wistar strain were fed a selenium-deficient diet, the activity of classic glutathione peroxidase (GPx) in liver cytosol decreased rapidly. In contrast, the activity of phospholipid hydroperoxide GPx (PHGPx) in the cytosol decreased only slowly. Despite the marked decrease in classic GPx activity, the lipid peroxide level in the liver did not change until 6 weeks after the start of the feeding, whereas the level was significantly increased by 9 weeks, by which time PHGPx activity and its protein level had markedly diminished. These data indicate that PHGPx is much more crucial than classic GPx in preventing the elevation of liver lipid peroxide level in selenium-deficient rats.

Animals↗
PubMed1990

Presenile (early ageing) changes in tissues of Kaschin-Beck disease and its pathogenetic significance.

The selenium level and activity of glutathione peroxidase in blood of children living in Kaschin-Beck disease (KBD) endemic areas were lower than that in nonendemic areas. KBD children were deficient in selenium, their lipid components, structure and function of the red cell membrane and cartilage tissue were abnormal. That is, the phospholipid (PL) content in the tissues of the patient was less than that of the controls in endemic and non-endemic areas. Especially as the phosphatidylcholine (PC) content decreased significantly, but sphingomyelin (SM) increased, the molar ratio of SM/PC and cholesterol (Ch)/PL increased. Increase of acanthocyte content was seen under the electron microscope and the fragility of erythrocytes was also increased. It indicated that there were membrane defects and membrane damage in KBD. At the same time, the sulfation extent of mucopolysaccharides in cartilage of patients was lower, and the collagen content was higher than that of controls. The presenile changes in lipid composition, structure and function of biomembranes and cartilage metabolism of KBD are very significant in studies on the aetiological pathogenesis of KBD and other ageing diseases.

Aging↗
PubMedDate not supplied

Characterization of chemoresistance mechanisms in a series of cisplatin-resistant transitional carcinoma cell lines.

We explored the mechanisms of cisplatin resistance in a series of bladder transitional carcinoma cells that are either sensitive or progressively resistant to cisplatin. Resistant lines were raised by chronic exposure of the parental cells to progressively increased concentrations of cisplatin. The cisplatin IC50s of the sensitive and the three resistant cells were 4.3, 25.0, 40.4, and 52.2 microM, respectively. The expressions of glutathione S-transferase pi (GST-pi) and multidrug resistance-associated protein (MRP) were enhanced in a dose-response manner as cells acquired progressive cisplatin resistance. Expression of mdr-1 transcript was detected in the three resistant lines but not in the sensitive line. Glutathione contents were increased in resistant cells, yet the trend of increase did not reach statistical significance (p = 0.061). In conclusion, transitional carcinoma cells may gain cisplatin resistance through multiple pathways including up-regulation of GST-pi, MRP and possibly mdr-1. Glutathione contents may play a less significant role in cisplatin chemoresistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗