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Biomedical subjects

Q Peng

Publications and source records attributed to Q Peng.

At least 127 records · Page 7Linked to original sources

Cytotoxicity and cytokinetic effects of mitomycin C and/or photochemotherapy in a human colon adenocarcinoma cell line.

1. The cytotoxicity and cytokinetic effects of Mitomycin C (MC) and/or photochemotherapy (PCT) in cultured human colon adenocarcinoma (WiDr) cells were investigated using colony formation to determine cell survival and DNA flow cytometry to analyze cell kinetics. 2. A low concentration of MC (0.01 micrograms/ml) caused accumulation of cells in late S and early G2 phase; higher concentrations (0.05-0.5 micrograms/ml) induced accumulation of the cells in mid and early S phase. 3. The effects of the lowest concentration of MC (0.01 micrograms/ml) were reversible upon removal of the drug, whereas a higher concentration of MC (0.1 micrograms/ml) resulted in a permanent inhibition of cell cycle progression. 4. The sensitivity of Photofrin II-loaded cells to PCT can be enhanced significantly by the addition of MC. 5. The MC-induced accumulation of the cells in S phase may be one reason for the increased cytotoxicity of PCT combined with MC. 6. The data suggest that MC may also inhibit repair of PCT-induced DNA damage.

Adenocarcinoma↗

[Effects of prostaglandin E2 on growth and function of osteoblasts in human cell culture in vitro].

The effects of prostaglandin E 2 (PGE2) on the differentiation and proliferation of osteoblasts (human fetal bone-cells) cultured in serum-free medium were investigated by assays of alkaline phosphatase (ALP) activity, intracellular cyclic AMP level and collagen synthesis in the cells. The results suggested that PGE2 in physiologic concentration stimulated the differentiation of osteoblasts in vitro, and might be involved in bone formation in vivo.

Alkaline Phosphatase↗

Subcellular localization, redistribution and photobleaching of sulfonated aluminum phthalocyanines in a human melanoma cell line.

Intracellular localization, intracellular translocation and photobleaching following non-lethal laser microirradiation of the fluorescing derivatives of sulfonated aluminum phthalocyanines (Al-PcSn, n = 1-4) in a human melanoma cell line (LOX) were studied by means of confocal laser scanning microscopy (LSM) and image processing. Use of confocal microscopy allowed 3-dimensional information to be obtained. Both Al-PcS1 and Al-PcS2 localized diffusely in the cytoplasm of the cells, while Al-PcS3 and Al-PcS4 exhibited a granular pattern in the extranuclear fraction of the cells. None of the Al-PcSn family was observed in the nuclei of the cells except that a small fraction of fluorescence was occasionally detected in nuclei of some cells treated with Al-PcS1 and Al-PcS2. Furthermore, exactly the same granular localization patterns and positions in the same cells were found after incubation initially with Al-PcS3 (or Al-PcS4) followed by acridine orange (AO) which emits red fluorescence from lysosomes of cells. Thus, the granular fluorescence of Al-PcS3 and Al-PcS4 is confined to the lysosomes of the LOX cells. Non-lethal laser exposure of cells incubated with high concentrations of the 2 dyes resulted in a translocation of the dyes from the lysosomes to the whole cytoplasm and an increase in total intracellular fluorescence intensity. Finally, a small fraction of the dyes localized into the nuclei of the cells. The laser exposure of cells incubated with low concentrations of the lysosomally localized dyes resulted in an increase in the intracellular fluorescence intensity with no translocation of the dyes. Under all conditions, high laser exposure resulted in a decrease in the total intracellular fluorescence intensity.

Cell Nucleus↗

Localization of potent photosensitizers in human tumor LOX by means of laser scanning microscopy.

By means of laser scanning fluorescence microscopy the intratumoral localization patterns of several photosensitizers in LOX tumors in nude mice were studied. Lipophilic dyes such as TPPS1 (tetraphenylporphine monosulfonate), TPPS2a (tetraphenylporphine disulfonates with the sulfonate groups on adjacent rings), AlPCS1 (aluminium phthalocyanine monosulfonate) and AlPCS2 (aluminium phthalocyanine disulfonates) localized mainly in tumor cells. The fluorescence intensity of these dyes increased from 4 h to 48 h postinjection and the fluorescence was still observable 120 h postinjection. The more hydrophilic dyes such as TPPS3 (tetraphenylporphine trisulfonates), TPPS4 (tetraphenylporphine tetrasulfonates), and AlPCS4 (aluminium phthalocyanine tetrasulfonates) localized mainly extracellularly in the tumorous stroma. The fluorescence intensity of these dyes decreased from 4 h to 48 h postinjection. 120 h postinjection no significant fluorescence of these dyes could be seen in the tumors. P-II (Photofrin II), 3-THPP [tetra(3-hydroxyphenyl)porphine], TPPS2o (tetraphenylporphine disulfonates with the sulfonate groups on opposite rings) and AlPCS3 (aluminum phthalocyanine trisulfonates) had a combined localization pattern, i.e. a strongly cytoplasmic membrane-localizing pattern and a weakly intracellular distribution pattern, although some fluorescence could be seen in the tumorous stroma. The data are discussed in relation to what is known about the in vivo photosensitizing efficiency of some of the dyes.

Animals↗

The effect of glucose administration on the uptake of photofrin II in a human tumor xenograft.

Athymic BALB/c nude mice, bearing a human melanoma LOX, were given the photosensitizing drug Photofrin II (10 mg/kg body wt.) intraperitoneally. The mice were also given one of the following chemicals intraperitoneally: glucose, galactose and glucose plus nordihydroguaiaretic acid (NDGA) which is an inhibitor of glycolysis. Multiple injections of glucose (3 g/kg body wt. given at -1, 0, +1 and +3 h relative to the injection of 10 mg/kg of Photofrin II at time 0) resulted in a significant increase in the uptake of Photofrin II in the tumor 4 h after a Photofrin II injection, while the uptake of Photofrin II in the other tissues remained unchanged. Administration of galactose had no significant effect on the uptake of Photofrin II in the tissues studied (tumor, muscle, skin and liver). NDGA seemed to abolish the effect of glucose injection.

Animals↗

Location of P-II and AlPCS4 in human tumor LOX in vitro and in vivo by means of computer-enhanced video fluorescence microscopy.

The patterns of in vitro intracellular and in vivo intratumoral localization of Photofrin II (P-II) and aluminum phthalocyanine tetrasulfonate (AlPCS4) in human melanoma LOX were studied by means of computer-enhanced video fluorescence microscopy (CEVFM). The hydrophobic drug P-II localized diffusely in the perinuclear fraction of the cytoplasm of the LOX cells cultivated in vitro. Light exposure did not result in any observable change in the localization pattern. The hydrophilic dye AlPCS4 was distributed as granular and grain patterns in the cytoplasm before light exposure, in exactly the same pattern as that of acridine orange incubated in the same cells, which is known to emit red fluorescence from lysosomes, thus indicating that AlPCS4 was also primarily localized in the lysosomes of the LOX cells. After light exposure the distribution of the intracellular AlPCS4 fluorescence was altered and the intensity increased. In vivo, P-II had a combined cellular localization pattern (i.e. a strongly cytoplasmic membrane-localizing pattern and a weakly intracellular distribution pattern) and an extracellular distribution pattern in the tumor tissue, while the AlPCS4 fluorescence was seen mainly in the stroma of the tumor. The total fluorescence intensity of P-II and AlPCS4 in the LOX tumor tissue at different times after injection was quantitatively determined by means of CEVFM.

Animals↗

Sensitizer for photodynamic therapy of cancer: a comparison of the tissue distribution of Photofrin II and aluminum phthalocyanine tetrasulfonate in nude mice bearing a human malignant tumor.

The distribution of Photofrin II (P-II) and aluminum phthalocyanine tetrasulfonate (AIPCS4) in tissues of BALB/c nu/nu nude mice bearing the LOX human melanoma was measured fluorimetrically at different times after intraperitoneal injection of the drugs, 20 mg/kg body weight. The plasma levels of the drugs as well as the excretion in feces and urine were also determined. The plasma concentrations of both drugs were found to build up in a similar manner during the first 30 min after injection. Thereafter, the plasma level of AIPCS4 decreased exponentially with an elimination half-life of 1.5 hr. The kinetics of elimination of P-II from the plasma were consistent with a 2-compartment model, with 90% of sensitizer lost with a half-life of about 5 hr, and the remaining fraction with a half-life of 30 hr. About 80% of the injected dose of P-II was excreted in the feces during the 7-days following injection, while 77% of AIPCS4 was excreted in the urine during the same period. After injection of a dose of 20 mg/kg, the concentrations of P-II in the LOX tumor as well as in the skin, muscle, brain, heart, lung, kidney and liver increased for about 24 hr, then remained constant or decreased slowly for the next 48 hr, after which they decreased slightly faster. On the other hand, the concentrations of APICS4 in most tissues as well as in the tumor peaked at about 30 min, then decreased with a half-life of between 1.5 and 3 hr. The tumor/skin concentration ratio was about 1 for both drugs (1-24 hr after injection). The tumor/muscle concentration ratio was about 2 for P-II at all sampling times, and maximally 10 (at 18 hr after injection) for AIPCS4. In the present tumor model, the tumor/tissue concentration ratio for all tissues at 1 hr and at 24 hr after the injection was equal for the 2 drugs or higher for AIPCS4.

Animals↗

Clinical and experimental observations on treatment of peptic ulcer with wei yang an (easing peptic-ulcer) capsule.

The therapeutic effects of peptic ulcer treated with cimetidine and Wei Yang An were compared clinically and experimentally by the double blind method. Results showed that the effects of the two are similar, but the long-term effect of Wei Yang An was better. Wei Yang An was also good for most cimetidine resistant ulcers, with few side effect. Animal experiment showed that Wei Yang An inhibited the ulcers.

Adult↗

Aluminum phthalocyanines with asymmetrical lower sulfonation and with symmetrical higher sulfonation: a comparison of localizing and photosensitizing mechanism in human tumor LOX xenografts.

A comparison of time-dependent localization patterns between lower, asymmetrical (AIPCS2a) and higher, symmetrical (AIPCS4) sulfonates of aluminum phthalocyanines in human malignant melanoma LOX transplanted to athymic nude mice from 1 to 120 hr after i.v. administration was made by means of laser scanning fluorescence microscopy. The lipophilic AIPCS2a was distributed mainly in tumor cells, while the hydrophilic AIPCS4 localized only in the vascular stroma of the tumor tissue. Concomitantly, comparative observations on the killing mechanism of photodynamic effects after treatment with a much lower i.v. dose of AIPCS2a and AIPCS4 plus laser light on the human tumor LOX were also made by morphological studies. Light and electron microscopy showed that there was a direct, extensive, photo-damaging action on all organelles and nuclear structure in the tumor cells after PDT with AIPCS2a; whereas the photo-induced injury to the tumor tissue after treatment with AIPCS4 and light was largely the consequence of initial functional vasogenic response and ultimate damage to vascular structure. These findings correlate well with the different localization patterns of the 2 dyes observed in human tumor tissues.

Animals↗

Localization of fluorescent Photofrin II and aluminum phthalocyanine tetrasulfonate in transplanted human malignant tumor LOX and normal tissues of nude mice using highly light-sensitive video intensification microscopy.

A comparative kinetic observation of the in vivo biolocalization of Photofrin II (P-II) and aluminum phthalocyanine tetrasulfonate (AIPCS4) in a transplanted human malignant tumor LOX and in normal tissues of nude mice has been made by means of highly light-sensitive video intensification microscopy at various intervals after i.p. administration. In the human tumor LOX, transplanted to athymic nude mice, fluorescence of P-II was observed on the membrane and in the cytoplasm of tumor cells, and in the stroma 4-48 hr post-injection. From 72 hr post-injection almost all fluorescing P-II had disappeared from the membrane of the tumor cells while strong fluorescence was still found in the stroma. AIPCS4 fluorescence was seen mainly in tumorous stroma with none detected in the tumor cells. Almost no fluorescence was found in the tumorous stroma 24 hr after injection. In most normal tissues observed, P-II was eliminated at a much slower rate than AIPCS4, but the in vivo biolocalization of the 2 drugs was similar. They were observed primarily where collagenous proteins are normally found, i.e. basal lamina, collagenous connective tissue, and in keratinized epithelium, renal epithelium, mononuclear phagocyte system and on the membrane of muscular cells. In addition, AIPCS4 had a strong affinity for the bronchiogenic epithelium. In the skin, P-II was distributed in keratinized epithelium, hair, hair follicles and their accessory, collagenous connective tissue of dermis, whereas AIPCS4 was present only in hair and collagenous connective tissue of dermis. No fluorescence of P-II or of AIPCS4 was found in the skin epidermis, nor in the transitional epithelium of the bladder mucosa.

Animals↗

Hematoporphyrin diethers--V. Plasma protein binding and photosensitizing efficiency.

1. Binding of added hematoporphyrin (HP) ethers to human plasma proteins and lipoproteins has been investigated by ultracentrifugation. 2. The binding to low density lipoproteins (LDL) has been discussed in terms of photosensitized tumor growth delay of tumors and HPLC-retention time, i.e. degree of polarity. 3. The LDL-binding data show a uniform relationship to sensitizing efficiency and degree of polarity, the only exception being HP-diamyl ether. No such uniform relationship exists for less related dyes, such as HP, tetraphenylporphyrin tetrasulfonate and HP-dimethyl ether.

Animals↗

Localization of potent photosensitizers in human tumor LOX by means of laser scanning microscopy.

By means of laser scanning fluorescence microscopy the intratumoral localization patterns of several photosensitizers in LOX tumors in nude mice were studied. Lipophilic dyes such as P-II (Photofrin II), 3-THPP tetra(3-hydroxyphenyl)porphin, TPPS1 (tetraphenylporphine monosulfonate), TPPS2a (tetraphenylporphine disulfonates with the sulfonate groups on adjacent rings), A1PCS1 (aluminium phthalocyanine monosulfonate) and A1PCS2 (aluminium phthalocyanine disulfonates) localized mainly in tumor cells. The fluorescence intensity of these dyes increased from 4 h to 48 h post-injection and the fluorescence was still observable 120 h post-injection. The more hydrophilic dyes such as TPPS2o (tetraphenylporphine disulfonates with the sulfonates groups on opposite rings), TPPS3 (tetraphenylporphine trisulfoantes), TPPS4 (tetraphenylporphine tetrasulfonates), A1PCS3 (aluminium phthalocyanine trisulfonates) and A1PCS4 (aluminium phthalocyanine tetrasulfonates) localized mainly extracellularly in the tumorous stroma. The fluorescence intensity of these dyes decreased from 4 h to 48 h post-injection. 120 h post-injection no significant fluorescence of these dyes could be seen in the tumors. The data are discussed in relation to what is known about the in vivo photosensitizing efficiency of some of the dyes.

Animals↗

Structure and activity of trypsin in reverse micelles.

The kinetic properties of trypsin have been studied in reverse micelles formed by two surfactant systems, namely bis(2-ethylhexyl) sodium sulfosuccinate (AOT) in isooctane, and hexadecyltrimethyl ammonium bromide (CTAB) in chloroform/isooctane (1:1, by vol.). Three substrates have been used, namely N alpha-benzoyl-L-Arg ethyl ester, N alpha-benzoyl-L-Phe-L-Val-L-Arg p-nitroanilide (BzPheValArg-NH-Np) in AOT and N alpha-benzyloxycarbonyl-L-Lys p-nitrophenyl ester (ZLysO-Np) in CTAB. One of the main aims of the work was to compare the behaviour of trypsin in reverse micelles with that of alpha-chymotrypsin, for which an enhancement of kcat had been observed with respect to aqueous solutions. The pH profile is not significantly altered in reverse micelles with respect to water, however the kinetic parameters (kcat and Km) differ widely from one another, and are markedly affected by the micellar conditions, in particular by the water content wo (wo = [H2O]/[AOT]). Whereas in the case of BzPheValArg-NH-Np kcat is much smaller than in water, in the case of ZLysO-Np at pH 3.2 (but not at pH 6.0) a slight enhancement with respect to water is observed. On the basis of rapid kinetic spectrophotometry (stopped-flow) and solvent isotope effect studies, this enhancement is ascribed to a change in the rate-limiting step (acylation rather than hydrolysis). As in the case of alpha-chymotrypsin, the maximal activity is found for all substrates at rather small wo values (below 12), which is taken to suggest that the enzyme works better when is surrounded by only a few layers of tightly bound water. Spectroscopic studies [ultraviolet absorption, circular dichroism (CD) and fluorescence] have been carried out as a function of wo. Whereas the absorption properties are practically unchanged, the CD spectrum in AOT micelles has a lower intensity than in water, which is interpreted as a partial unfolding. The intensity is partly restored when Ca2+ ions are added, indicating that the micellar environment may cause a partial denaturation by depleting it of calcium ions. Fluorescence data show that the emission properties of the protein in reverse micelles match those in aqueous solution at around wo = 13 approx., whereas lambda max shifts towards the red by increasing wo, indicating an exposure of the tryptophan residues and probably an unfolding of the whole protein, at wo values above 15. Finally the reaction between trypsin and its specific macromolecular Kunitz inhibitor from soybeans is studied.(ABSTRACT TRUNCATED AT 400 WORDS)

Calcium Chloride↗