GLORIA

GEOMAR Library Ocean Research Information Access

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • Liu, Qifa  (5)
  • Wang, Zhixiang  (5)
  • 1
    In: Oncotarget, Impact Journals, LLC, Vol. 6, No. 32 ( 2015-10-20), p. 33612-33622
    Type of Medium: Online Resource
    ISSN: 1949-2553
    URL: Issue
    Language: English
    Publisher: Impact Journals, LLC
    Publication Date: 2015
    detail.hit.zdb_id: 2560162-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 2
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 3647-3647
    Abstract: It is known that SCF/c-kit signaling pathway is one of the most important pathways in regulating of cell proliferation, differentiation and apoptosis, which can be continuously activated by C-KIT mutation and then lead to cell proliferation increase or apoptosis decrease. Furthermore, we have proven in our previous study that amyloid precursor protein (APP) gene, which is reported to increase cell proliferation in some solid cancer, is correlated with C-KIT mutation and adversely affects the disease outcome in AML1-ETO-positive acute myeloid leukemia (AML1-ETO-positive AML). In this study we focus on the regulation of cell proliferation and apoptosis in AML1-ETO-positive leukemia by APP gene and its mechanism. APP and C-KIT expression in bone marrow cells before the first chemotherapy from the 65 patients with AML1-ETO-positive AML (Blood. 2014,124:942) was simultaneously assessed by quantitative reverse transcriptase (QRT)-PCR method, meanwhile, the correlation of APP expression with peripheral WBC count, and the rate of bone marrow cellularity and blasts were observed. Furthermore, kasumi-1 cell line was chosen as cell model, and APP gene was knocked down using siRNA technology. The correlation of cell proliferation, differentiation and apoptosis with APP expression, as well as the regulation of SCF/c-kit signaling pathway by APP gene was analyzed on the cell line. WBC count and bone marrow cellularity, but not bone marrow blasts, was correlated with APP expression, in that a higher WBC count (29.2±3.9·109/L) was observed in APP-H patients when compared with 17.9±2.9·109/L in APP-L patients (P=0.008), and a higher percentage of bone marrow cellularity in APP-H patients (86.7%±1.7%) versus 80.3%±2.3% in APP-L cases (P=0.031). Moreover, the level of C-KIT mRNA expression was positively correlated with APP expression (r=0.349, P=0.011). In kasumi-1 cell line, compared with wild type and negative control cells, cell apoptosis, both early and late, increased significantly when APP gene was knocked down (Figure 1)., however, not apparently change was observed in cell proliferation and differentiation. What's more, C-KIT expression at both transcription (as evidenced by RTQ¨CPCR analysis) and translation (as confirmed by CD117 assay) levels, as well as BCL-2, C-KIT, p-ERK, p-AKT, P53 and NF-κB (as evidenced by western blot analysis, Figure 2), decreased significantly when APP was knocked down. In conclusion, APP gene involves in the regulation of cell apoptosis but not proliferation in AML1-ETO-positive leukemia via SCF/c-kit signaling pathway. Figure 1. Flow cytometry analysis of cell apoptosis in kasumi-1 cells with different APP expression. Both the rate of early (Q4-2) and late apoptosis (Q2-2) in si-APP kasumi-1 cell increased significantly when compared with the rate in wild type and NC kasumi-1 cell (Early apoptosis rate: si-APP: 29.00%±0.98%, wild type: 21.43%±0.86%, NC: 21.67%±0.78%, F=71.927, P 〈 0.001; Late apoptosis rate: si-APP: 19.80%±1.51%, wild type: 12.33%±0.75%, NC: 12.90%±1.25%, F=35.239, P 〈 0.001). Figure 1. Flow cytometry analysis of cell apoptosis in kasumi-1 cells with different APP expression. Both the rate of early (Q4-2) and late apoptosis (Q2-2) in si-APP kasumi-1 cell increased significantly when compared with the rate in wild type and NC kasumi-1 cell (Early apoptosis rate: si-APP: 29.00%±0.98%, wild type: 21.43%±0.86%, NC: 21.67%±0.78%, F=71.927, P 〈 0.001; Late apoptosis rate: si-APP: 19.80%±1.51%, wild type: 12.33%±0.75%, NC: 12.90%±1.25%, F=35.239, P 〈 0.001). Figure 2. Western blot analysis of the expression of BCL-2, C-KIT, p-ERK, p-AKT, P53 and NF-κB with different APP expression. Figure 2. Western blot analysis of the expression of BCL-2, C-KIT, p-ERK, p-AKT, P53 and NF-κB with different APP expression. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 3
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 4932-4932
    Abstract: Introduction. Most acute myeloid leukemia (AML) patients with adverse prognosis either fail to achieve complete remission (CR) or relapse after short-term remission, new strategies are needed to improve therapeutic effect in these patients. Gene silencing via DNA methylation are frequent and reversible in high-risk AML, it provides the possibility to treat AML patients with DNA-hypomethylating agent. Decitabine alone has limited anti-leukemia effect and minimal toxicity. Studies demonstrated that decitabine prior to chemotherapy was likely to increase efficacy in AML. In this study, we investigated the effect of decitabine on susceptibility to cytotoxic drugs in chemoresistant AML cells. Efficacy and safety of decitabine prior to HAA regimen was evaluated in refractory, relapsed and high-risk AML patients. Methods. HL60, HL60/ADR, Kasumi-1, and primary AML cells were pre-treated with 1.0 μM decitabine for 72 hours, Sensitivities to harringtonine, adriamycin, cytarabine and the combination was determined by MTT, apoptosis was analyzed by flow cytometry. Protein expression was detected by western blotting. In clinic, Twenty-three patients were enrolled in decitabine prior to HAA regimen, and twenty-four patients in HAA alone. CR ratio was used to evaluate efficacy. Durations of neutrocytopenia or thrombcytopemia and infection incidence were observed to assess the safety. All of patients were followed up to 36 monthes, overall survival (OS) and disease-free survival (DFS) were calculated. Result. Decitabine increased sensitivity and apoptosis induced by harringtonine in HL60/ADR, as well as adriamycin and cytarabine in HL60/ADR and Kasumi-1 cells. But no change in sensitivity to each drug was observed in HL60, and sensitivity to harringtonine in Kasumi-1. The similar changes in sensitivity to adriamycin and cytarabine were also observed in primary AML cells from refractory patients (n=6). Cytotoxic effect of HAA was alsoincreaed by decitabine in HL60/ADR and Kasumi-1 cells (p=0.004, 0.018). Western blotting showed that decitabine decreased expression of DNMT1, activation of p53 and inhibition of c-Myc, Survivin and Bcl-2. In clinic, 16 (69.6%) patients in decitabine plus HAA regimen responded to the first course of induction therapy: 14 CR (60.9%) and 2 PR (8.7%). 1 in 2 patients with PR achieved CR after second course induction. It brought the overall CR was 65.2%. Otherwise, 10 (45.8%) patients in HAA regimen alone responded to the first induction: 7 CR (29.2%) and 4 PR (16.7%), 3 in 4 patients with PR achieved CR after the second induction, and overall CR reached 41.7%. The first-cycle CR ratio in decitabine plus HAA was higher than that in HAA alone (p=0.041). Patients continued to receive chemotherapy alternatively combined with decitabine. The median OS was 14 months in chemotherapy plus decitabine, 6 months in chemotherapy alone, and median DFS were 18 and 5 months in the former and latter. No significant difference was observed in the time of neutrophil (p=0.832, 0.631) or platelet recovery (p=0.798, 0.544) after induction and intensification therapy. The incidences of infection were also similar (p=0.724, 0.697). The clinic data indicated that decitabine plus HAA regimenit was efficacy and well-tolerated to treat refractory AML patients. Conclusion. Our results demonstrated that decitabine increased cytotoxic effect against chemoresistant AML cells. Combination of decitabine and HAA was safe and efficacy to treat refractory/relapsed AML. These findings support clinic protocols based on decitabine prior to chemotherapy to overcome resistance and improve therapeutic efficacy in AML patients. Disclosures Carter: PrismBiolab: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 4
    In: Oncology Reports, Spandidos Publications, Vol. 36, No. 3 ( 2016-09), p. 1626-1632
    Type of Medium: Online Resource
    ISSN: 1021-335X , 1791-2431
    Language: English
    Publisher: Spandidos Publications
    Publication Date: 2016
    detail.hit.zdb_id: 1222484-4
    detail.hit.zdb_id: 2120548-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 5
    In: Oncology Letters, Spandidos Publications, ( 2017-11-13)
    Type of Medium: Online Resource
    ISSN: 1792-1074 , 1792-1082
    Language: Unknown
    Publisher: Spandidos Publications
    Publication Date: 2017
    detail.hit.zdb_id: 2573196-8
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...