Biomedical subjects

Qin Jiang

Publications and source records attributed to Qin Jiang.

13 recordsLinked to original sources

PubMed2006

DNA binding properties of novel cytotoxic gold(III) complexes of terpyridine ligands: the impact of steric and electrostatic effects.

Four gold(III) complexes of terpyridine derivatives 1-4 have been synthesized and characterized by spectroscopic methods. In vitro data demonstrated that all of them showed higher cytotoxicity than cisplatin against the human non-small-cell lung cancer cell line (A-549), the human stomach carcinoma cell line (SGC-7901), the human cervix carcinoma cell line (HELA), the human colon carcinoma cell line (HCT-116), the human liver carcinoma cell line (BEL-7402), the murine leukemia cell line (P-388) and the human acute promyelocytic leukemia cell line (HL-60). Complex 3 exhibits the highest activity, with growth inhibition rates of over 80% at 10(-8) mol L(-1) against the A-549, HCT-116 and HELA tumor cell lines. Interestingly, ligands L1-L4 are also very cytotoxic against the cell lines tested. Complexes 1-4 are stable in aqueous solution for 2 days in the presence of the biological reducing agent glutathione. The inductively coupled plasma mass spectrometry data showed that DNA isolated from cells treated with complexes 1 and 3 contained gold with gold-to-nucleotide ratios of approximately 1:6,400 and 1:4,900, respectively. Fluorescence titration, UV and circular dichroism analyses proved that the steric and electrostatic effects of the ligand remarkably influence the interactions of their gold(III) complexes with DNA. The DNA binding ability of the complexes has been correlated with their cytotoxicity, which could potentially provide a new rationale for the future design of terpyridine-based metal complexes with antitumor potential.

Cell Line, Tumor↗

PubMed2006

Gold(III) compounds of 1,4,7-triazacyclononane showing high cytotoxicity against A-549 and HCT-116 tumor cell lines.

Two gold(III) compounds [Au(TACN)Cl(2)]Cl (1) and [Au(TACN)Cl(2)][AuCl(4)] (2) (where TACN=1,4,7-triazacyclononane), have been synthesized and characterized by electrospray ionization mass spectrometry (ESI-MS), (1)H NMR spectroscopy and elemental analyses. The structure of compound 2 was determined by X-ray crystallography, in which TACN coordinates to the gold(III) center in a bidentate mode and the unbound amine group forms a very short intramolecular Au-H(-N) contact (1.91A). Biological activity data showed that compound 1 is more cytotoxic than cisplatin against A-549 and HCT-116 tumor cell lines. The interactions of compound 1 with CT-DNA were studied by UV-Vis, fluorescence and CD spectroscopy, which suggests that compound 1 can induce the distortion of DNA double helix.

Antineoplastic Agents↗

PubMed2006

Design and synthesis of 5-aryl-pyridone-carboxamides as inhibitors of anaplastic lymphoma kinase.

Anaplastic lymphoma kinase (ALK) is a promising new target for therapy of certain cancers such as anaplastic large-cell lymphoma (ALCL) and inflammatory myofibroblastic tumor (IMT). We have identified a series of novel pyridones as kinase inhibitors of ALK by application of a stepwise process involving in vitro screening of a novel targeted library followed by iterative template modification based on medicinal chemistry insights and computational ranking of virtual libraries. Using this process, we discovered ALK-selective inhibitors with improved potency and selectivity. Herein the details of the design process and synthesis of these novel pyridones, along with their enzymatic and cell-based activity, are discussed.

Amides↗

PubMed2006

EGF-induced cell migration is mediated by ERK and PI3K/AKT pathways in cultured human lens epithelial cells.

Cataract is considered as the most common cause of blindness, which is curable only by surgery. Postsurgery, however, many patients gradually develop the complication of posterior capsule opacification (PCO) or secondary cataract, arising from stimulated cell proliferation and cell migration within the lens capsule. The migration of human lens epithelial cells (HLECs) plays crucial roles in the remodeling of lens capsule and cataract formation, but less is known about the cell-signaling mechanism of migration. We observed that epithelial growth factor (EGF) induced cell migration in cultured human lens epithelial cells through the ERK and PI3K/AKT pathways. EGF induced cell migration in a dose-dependent manner; EGF-induced EGFR phosphorylation and downstream activation of c-Jun N-terminal protein kinase (JNK), p38 MAP kinase (p38), extracellular signal-regulated kinase (ERK1/2) and AKT, were inhibited by PD153035 (EGFR inhibitor), JNKi (JNK inhibitor), SB203580 (p38 inhibitor), U0126 (MEK/ERK inhibitor), and LY294002 (PI3K/AKT inhibitor), respectively. Furthermore, we found that EGF induced activity of matrix metalloproteinase-2 (MMP-2) in cultured HLECs. EGF-induced MMP-2 activity was significantly inhibited by treatment of PD153035, U0126, and LY294002, but not SB203580 and JNK inhibitor, suggesting that ERK and the phosphatidylinositol-3-kinase (PI3K)/AKT pathways selectively mediate EGF-stimulated MMP-2 activity and cell migration in cultured HLECs in vitro. Taken together, our results suggest that the cell-signaling pathways involved in EGF-stimulated cell migration may constitute potential therapeutic targets in the treatment of PCO.

Cell Line↗

PubMed2006

UV radiation down-regulates Dsg-2 via Rac/NADPH oxidase-mediated generation of ROS in human lens epithelial cells.

Ultraviolet radiation-induced cataract has been believed to be associated with degradation of cellular components. We report that, in cultured human lens epithelial cells, UV radiation analogous to H2O2 treatment down-regulates desmosomal protein desmoglein-2. UV radiation induces generation of reactive oxygen species and transiently activates epidermal growth factor receptor, which in turn induces translocation of Rac2 and NADPH oxidase activity. Collectively, our data demonstrate that UV-induced desmoglein-2 down-regulation is mediated reactive oxygen species which are generated through EGFR activation and Rac2/NADPH oxidase activation, suggesting that antioxidants may be applied for protection against UV-induced cataract.

Animals↗

PubMed2006

[Research in the relation between telomerase reverse transcriptase expression in spermatogenic cells and serum levels of estradiol of fluorotic rats].

OBJECTIVE: To study the relation between telomerase reverse transcriptase (TERT) activity expression in spermatogenic cells and serum levels of estradiol of fluorotic rats. METHODS: We randomly divided thirty SD male rats into control group, low-dose group and high-dose group, then inject sodium fluoride (0, 10, 20 mg/kg bw) into celiac of rats. We respectively observed changes of estrogen and TERT using methods of radioimmunoassay, in situ hybridization. In addition, we observed the quality of spermatozoa. RESULTS: The level of estrogen, the expression of telomerase and the number and the livability of the spermatozoon in low-dose and high-dose fluorotic rats were lower than those of control rats (P < 0.05). Therefore,the above indexes decreased with the increase of dosage. In addition, sperm aberration of each fluorotic group was higher than control group (P < 0.05). And it increased with the increase of dosage. The content of E2 in serum of different fluoride treatment groups was positively correlated with the expression of telomerase in seminiferous tubule significantly, respectively (low-dose fluoride treatment groups, r = 0.941, P < 0.01, high-dose fluoride treatment groups, r = 0.929, P < 0.01). CONCLUSION: NaF possibly damaged the male reproductive system by the approach of E2/ER-TERT-spermatozoon, relation between TERT expression in spermatogenic cells and serum levels of estradiol is positive correlation.

Animals↗

PubMed2005

Relationship between the downregulation of HLA class I antigen and clinicopathological significance in gastric cancer.

AIM: To discuss the expression of human leukocyte antigen (HLA) class I antigens in gastric cancer and correlate these with pathologic type and TNM stage. METHODS: The expression of HLA class I antigen was detected by immunohistochemistry in 185 specimens of gastric cancer, 20 gastric cancer specimens with lymphatic metastasis and 22 controls of normal gastric mucosa using four monoclonal antibodies. RESULTS: The expression of HLA class I antigen (B/C locus) was significantly downregulated in gastric cancer and in lymphatic metastasis than that in normal gastric mucosa (chi2=7.712, P<0.05). The expression of other HLA class I antigens was also downregulated, but the change was slight. There was no relationship between the downregulation of HLA class I antigen and that of beta2m and LMP2. The expression of HLA class I (B/C locus) was statistically correlated with pathologic stage in gastric adenocarcinoma (chi2=4.164, P<0.05). CONCLUSION: The expression of HLA class I antigen (B/C locus) was obviously downregulated in gastric cancer and in lymphatic metastasis. This abnormal expression would provide the tumor cells with a way to avoid immunological recognition.

Adult↗

PubMed2005

Antidepressant-like effects of BCEF0083 in the chronic unpredictable stress models in mice.

BACKGROUND: Up to now there have been no satisfactory drugs to treat psychiatric disorders, and now bioactive compound from entomagenous fungi (BCEF0083) is a new type of bioactive compound from entomopathogenic fungi. Our previous investigations have shown that BCEF has an inhibition effect on monoamine oxidase. So, BCEF may be a latent antidepressant. This study aimed at observing the antidepressant effects and its mechanism of BCEF in the chronic unpredictable stress models in mice. METHODS: The antidepressant effects of BCEF were examined on the chronic unpredictable stress models in mice. Sixty mice were randomly divided to six groups. Animals were housed and isolated except saline group. Mice were exposed to different stressors per day randomly from day 1 to day 21. Body weight were weighed on day 1, day 10 and on day 21 during the 21-day stress procedure. Awarding response was detected by using method of calculating the 24-hour consumption of saccharum water. Step through test was used to evaluate the behavioral response. AVP contents in plasma were also detected by using radioimmunoassays. RESULTS: Chronic unpredictable stress resulted in a significant decrease of the body weight and could apparently cause escape behavior disturbance and gradual reduction of sensitivity to reward in animal models. Drug treatment (BCEF 25, 50, 100 mg/kg) could significantly ameliorate the decreased body weight and effectively reverse the escape behavior disturbance. The gradual reduction of sensitivity to reward, the anhedonic state, was also effectively reversed by BCEF. BCEF (50, 100 mg/kg) could also effectively restore the AVP content in the plasma. CONCLUSIONS: This evidence suggests that BCEF can effectively inhibit the depression behavior and show strong antidepressant effect. BCEF can effectively restore the plasma AVP release and this may be an important mechanism of its antidepressant effect.

Animals↗

PubMed2005

Transient activation of EGFR/AKT cell survival pathway and expression of survivin contribute to reduced sensitivity of human melanoma cells to betulinic acid.

Betulinic acid (BA), a pentacyclic triterpene first identified less than a decade ago, has served as a melanoma-specific cytotoxic agent, and yet its specificity is being challenged. Recently, we found that human melanoma cells exhibited less sensitivity to betulinic acid than human skin keratinocytes. This study was designed to investigate the cell signaling pathway leading human melanoma cells to increased resistance to betulinic acid treatment. In vitro experiments using cultured human melanoma cells indicated that betulinic acid transiently induced survivin expression. The expression of survivin started 30 min post-betulinic acid treatment, peaked at 2 h, remained elevated for 8 h and returned to basal level within 24 h. Similarly, epithelial growth factor (EGF) treatment induced expression of survivin in a time-dependent manner. Since epithelial growth factor receptor (EGFR) activation leads to the activation of cell signaling components that are important to cell survival, we next examined whether BA-induced survivin expression is mediated by the EGFR pathway. The results showed that BA induced EGFR tyrosine phosphorylation in a time-dependent manner. Further, BA strongly induced AKT phosphorylation in a similar pattern. AKT activation started 15 min post-treatment, peaked at approximately 1 h, remained elevated for 4 h and returned to basal level within 8 h. BA also induced ERK activation and, in contrast, weakly induced JNK and p38 activation. Pretreatment of EGFR inhibitor PD153035 blocked BA-induced EGFR phosphorylation, ERK and AKT activation, and survivin expression. Results of the MTT dye assay showed that a combination of PD153035 and BA enhanced melanoma cell death. Collectively, we conclude that betulinic acid transiently activated the EGFR/AKT cell survival pathway and induced survivin expression, contributing to less sensitivity in human melanoma cells. The data suggest that a combination of the EGFR inhibitor and betulinic acid may be a better clinical option to treat human melanoma.

Animals↗

PubMed2005

Targeted inhibition of transient activation of the EGFR-mediated cell survival pathway enhances paclitaxel-induced ovarian cancer cell death.

Emerging studies have suggested that transient activation of the cell survival pathway may be the strategy for cancer cells to fight against chemotherapy and eventually mysteriously evade paclitaxel-induced cell death. Modulation of the EGFR-mediated survival pathway in addition to the utilization of paclitaxel renders a promise of better clinical management. The objective of this study was to understand the molecular mechanism of transient induction of EGFR-mediated cell survival by paclitaxel. We utilized ovarian cancer cell line, Caov3, cells to investigate the effect of paclitaxel on EGFR-mediated MAP kinase and AKT activation, and the expression of survivin. We found that paclitaxel transiently induced EGFR phosphorylation and ERK and AKT activation but not JNK and p38. Paclitaxel-induced ERK and AKT activity was inhibited by the EGFR inhibitor, PD153035; ERK inhibitor, U0126; and PI3 kinase inhibitor, LY294002, respectively. We observed that paclitaxel transiently induced expression of survivin in the early hours of treatment. Paclitaxel-induced survivin expression was inhibited by the EGFR inhibitor, PD153035. Inhibitors of EGFR, ERK and PI3 kinase all enhanced paclitaxel-induced cell death. We conclude that paclitaxel transiently transactivates EGFR, leading to activation of cell survival factors, such as ERK and AKT, and expression of survivin, which are all inclusively accountable for ovarian cancer cell resistance to paclitaxel treatment. A combination of these inhibitors with paclitaxel may be a better option for ovarian cancer treatment.

Antineoplastic Agents, Phytogenic↗

PubMed2004

The diazo ketone approach to the isoprostanes.

A general synthetic approach to the isoprostanes has been established, based on intermolecular aldol condensation of a diazo ketone with an unsaturated aldehyde, followed by cyclization of the resulting diazo ketone to the cyclopropane. Subsequent kinetic opening with thiophenol followed by further elaboration then leads to the isoprostane. The history of this approach and the details of its development are discussed.

Isoprostanes↗

PubMed2003

[Clinical results of advanced gastric cancer patients treated with oxaliplatin-containing regimen].

BACKGROUND & OBJECTIVE: In vitro clinical research showed oxaliplatin (L-OHP) could obviously suppress the growth of gastric cancer cells in combination with most anti-cancer drugs and help these drugs to kill the tumor cells. This study was designed to evaluate the response and tolerance of oxaliplatin,leucovorin (LV), 5-fluorouracil (5-FU),and etoposide (VP-16) as first-line regimen in advanced gastric cancer, and compare with traditional chemotherapy regimen. METHODS: Forty-eight patients with advanced gastric cancer were divided into treatment group (L-OHP+LV+5-FU+VP-16) and control group(DDP+LV+5-FU+VP-16) using non-randomized method. L-OHP:135 mg/m(2), iv infusion 2 hours, d1(or DDP 20 mg, iv infusion, d1-5); LV:200 mg,iv infusion,d1-5; 5-FU:500 mg/m(2) CI 6 hours on d1-5; VP-16: 100 mg, iv infusion d1-5. Every course lasted 3-4 weeks. RESULTS: The response rate was 64% (16/25) in treatment group (25 cases) and 34.8% (8/23) in control group (23 cases). The statistic difference was seen in two groups (P< 0.05, Chi-square test). The median survival and 1-year survival rate were 11.5 months and 45.6% for treatment group versus 10.5 months and 36.5% for control group. There was no statistical difference in two groups for overall survival (P >0.05, log-rank test). The main side effects were sensory neuritis in treatment group and nausea vomiting in control group. There were significant statistically differences in two groups (P< 0.05, Wilcoxon rank sum test). The other side effects were similar. CONCLUSION: L-OHP + VP-16 + LV + 5-FU regimen is effective and well tolerable for advanced gastric carcinoma.

Adult↗

PubMed2002

Synthesis of (-)-calicoferol B.

The first total synthesis of (-)-calicoferol B (III) is described. The cyclozirconation product I, prepared in enantiomerically pure form, was converted into the CD ring chiron II. This was coupled with the aromatic A-ring, and then the side chain was constructed with control of relative and absolute configuration to complete the total synthesis of III. The first total synthesis of (-)-calicoferol B (1) is described. The cyclozirconation product 8, prepared in enantiomerically pure form, was converted into the CD ring chiron 6. This was coupled with the aromatic A-ring, and then the side chain was constructed with control of relative and absolute configuration to complete the total synthesis of 1.

Aldehydes↗