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Biomedical subjects

R Han

Publications and source records attributed to R Han.

At least 55 records · Page 3Linked to original sources

[In vitro study on the effects of the novel retinoids combined with IFN-gamma on the proliferation and differentiation of fresh acute monocytic leukemic cells].

OBJECTIVE: To investigate the prospect for clinical use of novel retinoids YS 904012 and R 9158 in combination with IFN-gamma in inducing differentiation of acute monocytic leukemia. METHODS: The effects of novel retinoids with IFN-gamma on the differentiation and clonal proliferation of fresh leukemia cell from 6 monocytic leukemia patients were studied in vitro. Cell morphological examination, nitro tetrazolium blue reduction test and DCE, expression of CD14 and CD68 and CFU-L were used in the study. RESULTS: The primary leukemia cell, cultured with the combination of YS 904012 and IFN-gamma, became more mature in morphology. The NBT reduction rate and DCE were increased from 23.4% and 25.0% to 61.5% and 52.0%, respectively. The expression of CD14 and CD68 was increased. The growth of the leukemic colony in semi-solid culture was markedly inhibited. The activity of YS 904012 combined with IFN-gamma in inhibiting proliferation and inducing differentiation of monoblast was greater than that of R9158 or all-trans retinoic acid in combination with IFN-gamma (P < 0.01). CONCLUSION: The YS 904012 combined with IFN-gamma is worthy of further study for clinical differentiation therapy of acute monocytic leukemia.

Adult↗

[Inhibition of tumor invasion by new retinoid, 5-4A, and its mechanism of the action].

OBJECTIVE: To investigate the effect of 5-4A on the invasion of B16BL6 and to explore its mechanisms of action. METHODS: The invasion of B16BL6 was studied using the reconstituted basement membrane invasion assay. RESULTS: The phenotype of B16BL6 cells was obviously suppressed by 5-4A at the concentration of 4 x 10(-5) mol/L, and the inhibitory rate was 33.9%. CONCLUSION: 5-4A can inhibit invasion of B16BL6 cells and its mechanisms of action might be associated with the suppression of movement of tumor cells, decrease in the expression of type IV collagenase, and reversion of the phenotype of B16BL6 cells.

Animals↗

[Protein tyrosine kinase inhibitor genistein suppresses in vitro invasion of HT1080 human fibrosarcoma cells].

OBJECTIVE: To investigate the effects of genistein on cancer invasion and associated cellular characteristics and explore the possibility of developing protein tyrosine kinase inhibitors as anti-metastasis drugs. METHODS: HT1080 human fibrosarcoma cells were exposed to 20 mumol/L or 40 mumol/L genistein for 3 days. The abilities of the genistein-treated cells to invade through reconstituted matrigel or migrate through polycarbonate filters in transwell chambers were then investigated. Northern blot and laser densitometry were used to estimate the relative mRNA amounts of MMP-2, MMP-9 and TIMP-1 in the cells. RESULTS: The ability of the genistein-treated HT1080 cells to invade the reconstituted basement membrane was decreased significantly (P < 0.01). In consistent with the lowered invasive potential, migration rates of the drug-treated cells decreased dramatically. genistein did not, however, significantly affect attachment of HT1080 cells on fibronectin, laminin or Matrigel. Though exposure to genistein led to a small increase in MMP-2 and MMP-9 gene expression, a much greater increase in the amount of TIMP-1 mRNA was observed. Imbalanced enhancement of gene expression between matrix metalloproteinases and their inhibitors in favor of the latter may imply that matrix degradation is impaired in the genistein-treated cells. CONCLUSION: Genistein suppresses invasion of HT1080 cells at relatively low concentrations. genistein and other protein tyrosine kinase inhibitors might be valuable candidate drugs for the treatment of invasion and metastasis of cancer.

Antineoplastic Agents↗

[Apoptosis inductive effect of homoharringtonine and isoharringtonine on human acute promyelocytic leukemia HL-60 cells].

OBJECTIVE: To study the effects of homoharringtonine and isoharringtonine on the induction of apoptosis on human promyelocytic leukemia HL-60 cells. METHODS: By using flow cytometry, DNA gel electrophoresis, microscopy and electron microscopy. RESULTS: It was demonstrated that homoharringtonine and isoharringtonine can induce apoptosis of HL-60 cells significantly and rapidly. The activity of homoharringtonine was higher than that of isoharringtonine, and it was time and concentration dependent. CONCLUSIONS: Both homoharringtonine and isoharringtonine could induce apoptosis of HL-60 cells in terms of morphology, and DNA ladder assay. The activity of homoharringtonine was much higher than that of isoharringtonine.

Apoptosis↗

Effects of genistein on invasion and matrix metalloproteinase activities of HT1080 human fibrosarcoma cells.

Effects of genistein on invasion and matrix metalloproteinase activities were investigated in HT1080 human sarcoma cells. Invasion of HT1080 cells through reconstituted basement membrane was inhibited when the cells were treated with 100 micromol/L and 200 micromol/L genistein. At the same concentrations, genistein not only suppressed latent forms of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9) to convert into active forms, but also increase dramatically the tissue inhibitor of metalloproteinase (TIMP-1) mRNA contents and reverse the imbalance of MMPs and TIMPs. However, expressions of MMP-2 and MMP-9 were not significantly affected. Suppression of MMP activation and increase of TIMP-1 expression will decrease matrix degradation by MMPs, and consequently inhibit invasions of the cells. These results emphasized the existence of the imbalance between MMPs and TIMPs in tumor invasion and metastasis formation. The value of genistein as a drug for antiinvasion and anti-metastasis chemotherapy was suggested.

Antineoplastic Agents↗

Interobserver variability in 99mTc-DMSA renal scintigraphy reports: multicentric study.

BACKGROUND: The aim of the study was to evaluate the interobserver variability and reproducibility of the renal scintigraphy reports. METHODS: The study was prospective performed in 60 99mTc DMSA scintigraphies (116 kidneys), done in one centre, displayed on X ray films as analogue 300 kcounts images in 4 standard projections. Six observers from 4 different centres (group A), including three observers from one institution (group B), were asked to interpret original scans. Seven parameters of scintigraphy protocol were analysed with at least two responses: kidney size (1), uptake (2), outlines (3), scars (4), SOL (5), differential function (6) and conclusion (7). RESULTS: Among 116 kidneys, concordant results in interpretation of seven points of report from 1 to 7, in the group A were found in 62%, 42.5%, 45%, 9%, 47%, 52% and 34%, and In the group B in 72%, 55%, 59%, 22%, 62%, 60% and 41% respectively. Some improvement in concordant reporting was noted in the group of 3 observers, in comparison of group of all, statistically significant in category of scar reports (p < 0.01). CONCLUSIONS: Results suggest to use of standardised criteria and terminology in interpretations, to improve low interobserver reproducibility and objectivity of renal scintigraphy reports, particularly in evaluation of renal scars.

Journal Article↗

[Spectrophotometric assay of polyethyene glycol in urine using ammonium ferrothiocyanate aqueous-chloroform system].

A spectrophotometric method for the quantitative determination of polyethylene glycol-600 (PEG-600) in urine is based on partitioning a chromophore present in ammonium ferrothiocyanate reagent into an aqueous phase and a chloroform phase in the presence of PEG. The method is simple and reproducible, and can detect PEG in a concentration of 0.25 g/L. It gives a linear response over a range of 0.25-2.5 g/L. The recovery of PEG-600 in urine is 107% and relative standard deviation is less than 5%.

Chloroform↗

Characterization of transformation function of cottontail rabbit papillomavirus E5 and E8 genes.

Cottontail rabbit papillomavirus (CRPV) induces rabbit skin papillomas, which progress to invasive carcinoma in some animals. Two early genes, E7 and E6, have been demonstrated previously to be oncogenes. In this study, we identified two additional transforming genes, E8 and E5. Both E8 and E5 stimulated C127 and BALB/c A31 (A31) cell proliferation and affected cell cycle transition. The E8 and E5 transfectants lost cell contact inhibition, reaching a high saturation density when cultured up to 2 weeks. E8-C127 transfectants formed colonies in soft agar in the presence of platelet-derived growth factor (PDGF) while E5-C127 transfectants formed colonies without the requirement for PDGF. E8-C127 transfectants were highly tumorigenic whereas E5-C127 transfectants showed a weak tumorigenicity in nude mice. Both E8 and E5 A31 transfectants failed to form colonies in soft agar even in the presence of platelet-derived growth factor (PDGF) and did not develop tumors in nude mice. These results clearly showed that CRPVE8 and E5 are oncogenes and that the PDGF beta-receptor signaling pathway may be involved in E8-mediated C127 cell transformation. The difference in colony formation in soft agar and tumorigenicity in nude mice between C127 and A31 cell lines indicates that additional alterations in cellular gene expression are needed for E5- and E8-transfected cells to acquire a malignant phenotype.

3T3 Cells↗

H+ISFET-based biosensor for determination of penicillin G.

A biosensor based on an H+ ion sensitive field effect transistor (H+(-)ISFET) and penicillin G acylase has been developed. The response time of the sensor to different concentrations of penicillin G was 30 s. In a 20 mM phosphate buffer at pH 7.0, the linear range of the calibration curve was from 0.5 to 8 mM. The coefficients of variation for three samples with 20 repeated measurements were below 5%. Stability of the sensor could reach about 6 months and more than 1000 runs were performed without a significant decrease of the output value. The sensor was tested for measurement of the penicillin G content in penicillin fermentation both. Forty samples with low and high concentrations of penicillin G were chosen for the correlation test. The values assayed by the sensor method were compared with the values assayed by HPLC method, the correlation coefficient (r) was 0.9944 and the regression equation was y = 1.034X - 2083.7, respectively. The different measuring methods are discussed in the text.

Biosensing Techniques↗

Genistein suppresses adhesion-induced protein tyrosine phosphorylation and invasion of B16-BL6 melanoma cells.

Protein tyrosine phosphorylation occurs as one of the earlier events in cancer cell-extracellular matrix (ECM) interaction. With immunoblot analysis and immunofluorescence microscopy, genistein was found to suppress the tyrosine phosphorylation of proteins located at the cell periphery, including a 125 kDa protein, when B16-BL6 melanoma cells attached to and interacted with ECM. When accompanied by the suppression of adhesion-induced protein tyrosine phosphorylation, the invasive potential of B16-BL6 cells through reconstituted basement membrane was decreased significantly. However, neither adhesive capability nor cell growth was significantly affected by genistein. Therefore, the interruption of cancer cell-ECM interaction by suppression of protein tyrosine phosphorylation may contribute to invasion prevention of genistein.

Animals↗

[Binding activity of retinoids with recombinant human retinoic acid receptor RAR alpha].

OBJECTIVE: To establish a model for the rapid screening of differentiation-inducing agents. METHODS: Human RAR alpha cDNA was cloned into the PT7-7 plasmids and the human recombinant RAR alpha protein was expressed in Escherichia coli. The ligand-binding activity of the receptor with all-trans retinoic acid was studied by competitive binding assay. For comparison of the binding activity, five retinoids, with different activities and chemical structures, were chosen. The binding of these retinoids to RAR alpha was investigated and compared with the NBT reduction and acid phosphatase activity of HL-60 cells induced by these compounds. RESULTS: The binding activity of these retinoids was well correlated to their ability to induce differentiation of HL-60 cell line. CONCLUSION: This model could be used to screen differentiation-inducing agents.

Acid Phosphatase↗

[Induction differentiation by a new third generation retinoid R9158 on human acute promyelocytic leukemia cell line, NB4].

OBJECTIVE: In order to investigate the differentiation of 3',5'-ditertiary-butiary-4'-methoxy-carboxyl chalcone (R9158) on the acute promyelocytic leukemia NB4 cells. METHODS: By inditifying the function, morphology and karyotype of NB4 cells induced by R9158. RESULTS: Our results showed that R9158 or all-trans retinoic acid (RA) significantly inhibited the growth and colony formation of acute promyelocytic leukemia NB4 cells, while NBT-reduction (a functional differentiation marker of granulocytic) was dramatically increased when the cells were exposed to R9158 at 10(-9)-10(-6) mol/L, and the NBT positive cells reached about 97.5% at 10(-6) mol/L after 6 days expouse. The ED50 of NBT-reduction was achieved at concentration of 3.9 x 10(-9) mol/L and 2.8 x 10(-9) mol/L for R9158 and RA, respectively. Morphologically, most of the cells induced by R9158 and RA at 10(-6) mol/L were in the myelocytic or metamyelocytic stage and a few cells were in the banded or segmented stage. Cytogenetic analysis revealed that the karyotype of NB4 cells was subtetraploid and the chromosome numbers were in the range of 71-99, when NB4 cells were treated with R9158 or RA for 3-6 days, the abnormal polyploid chromosome numbers decreased to 72.9 +/- 6.9 (P < 0.01) or 68.5 +/- 7.0 (P < 0.01), but the t(15;17) translation did not disappear. CONCLUSIONS: R9158 has significant effects on the differentiation of NB4 cells.

Aneuploidy↗

[Anti-invasion activity of several plant-originated anticancer drugs with different mechanism of action].

The antitumor and anti-invasion activities of taxol, harringtonine, homoharringtonine and camptothecin on highly metastatic melanoma B16-BL6 and human fibrosarcoma HT-1080 cells were reported in this paper. Results demonstrated that taxol, harringtonine, homoharringtonine and camptothecin exhibited significant inhibition of cell growth of B16-BL6 and HT-1080 cells. Taxol, harringtonine and homoharringtonine were also found to be effective for the inhibition of cell invasion and migration of B16-BL6 cells, but camptothecin showed basically no effect at the indicated concentration.

Animals↗

[A new method for study of the effect of drugs on cancer cells--31PNMR with perfused cell system].

31P NMR was performed for the studies on the metabolic changes of endogenous phosphorus-containing molecules in KB and HCT-8 cells exposed to taxol at a concentration of 10(-6) mol.L-1. Using the perfusion method, the cells can be detected for a longer time by NMR, so as to give continuous spectra of the two cell-lines during the perfusion with and without the drug. The spectra showed that the levels of ATP peaks for both cells enhanced during the perfusion with the drug, but the change of the level is more prominent in KB cells than in HCT-8 cells. This shows that KB cells are more sensitive to taxol than HCT-8 cells. This is in coincident with the result in the cytotoxicity studies. However, the experiment using vincristine at the same concentrations demonstrated that the level of the ATP peak was not changed significantly.

Adenosine Triphosphate↗

[Isoharringtonine induces apoptosis in human leukemia HL-60 cell].

Harringtonine (HT), homoharringtonine (HHT) and isoharringtonine (IHT) are cephalotaxine alkaloids with anticancer activities which were isolated from Cephalotaxus hainanensis indigenous to China. Since the 1970s, HT and HHT have been developed as effective anticancer drugs in China and have been used widely in the treatment of acute nonlymphoid leukemia and chronic granulocyte leukemia. Although IHT has the advantage of low toxicity, it has not been developed as an anticancer drug because of its very low content in the plant. The cell apoptosis induced by isoharringtonine was investigated in human acute promyelocytic leukemia HL-60 cells by agarose gel electrophoresis of DNA, flow cytometry and transmission electron microscopy. In these experiments IHT showed significant and rapid apoptotic inductive effect on HL-60 cells in both concentration- and time-dependent fashion. The characteristic apoptosis-related features could be seen in IHT treated HL-60 cells. Transmission electron microscopy of IHT treated HL-60 cells displayed chromatin condensation and aggregation under the nuclear membrane, nuclear fragmentation and apoptosis body formation. Typical DNA ladder in agarose gel electrophoresis and pre-G1 peak in flow cytometric analysis were also observed in the cells exposed to IHT. The apoptotic rate could reach 43.8% in the HL-60 cells treated for 120 minutes with IHT 10(-7) mol.L-1. The cytotoxicity of IHT paralleled with cell apoptosis indicating that the anticancer activity of IHT results from the induction of apoptosis. These results are important impetus for further research and development of IHT as an anticancer agent.

Antineoplastic Agents, Phytogenic↗

[Effect of d-limonene, Salvia miltiorrhiza and turmeric derivatives on membrane association of Ras gene product and gap junction intercellular communication].

Gap junction intercellular communication (GJIC), H-ras oncogene expression and Ras oncogene product(P21ras protein) expression were studied in four human solid tumor cell lines, W1-38, CACO2, A549 and PaCa (with the different Ras gene mutation rate), and the effects of four compounds, Salvia miltiorrhiza derivative (SMD), d-limonene, turmeric derivative I(TD-I) and turmeric derivative II(TD-II), on them. The abilities of the four solid tumor cell lines to transfer dye to adjacent cells were examined using the scrape-loading/dye transfer technique, and the H-ras oncogene expression by Northern blotting and P21ras protein expression by Western blotting. The results showed the loss of intercellular coupling in PaCa cells, slight GJIC in A549 and CACO2 cells, and good GJIC in W1-38 cells. The four compounds used was shown to improve the GJIC of PaCa to different extents. The amount of total and membrane associated P21ras in PaCa cells were decreased after treatment with SMD, d-limonene and TD-I(2.5 micrograms.ml-1) for 48 h. Concomitantly, the growth of PaCa cells decreased in soft agar and GJIC was enhanced. The relative potency was found to be: d-limonene > SMD > TD-I = TD-II. No significant effect of the four compounds on H-ras oncogene expression was observed. These results suggest that 1. there was an excellent correlation between loss of Lucifer Yellow dye transfer and ras gene mutation rate in the four solid tumor cell lines used (ras gene mutation rate inversely correlated with average cell number couplied, r = 0.98) i.e., showing that high ras gene mutation is closely correlated with loss of GJIC in these malignant human tumor cells; 2. the antitumor effect of the monoterpene d-limonene and the phenol compound, SMD, might be related to the inhibition of P21ras membrane association and enhancement of GJIC, whilst that of the others may be by a different mechanism; 3. the inhibition of P21ras membrane association is directly related to the enhancement of gap junction intercellular communication.

Antineoplastic Agents, Phytogenic↗