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Li Shau-Hsuan Lu Hung-I Huang Wan-Ting Chen Yen-Hao Lo Chien-Ming Lan Ya-Chun Lin Wei-Che Tsai Hsin-Ting Chen Chang-Han 《Cancer cell international》2018,18(1):1-11
Breast cancer has been the first death cause of cancer in women all over the world. Metastasis is believed to be the most important process for treating breast cancer. There is evidence that lncRNA MEG3 functions as a tumor suppressor in breast cancer metastasis. However, upstream regulation of MEG3 in breast cancer remain elusive. Therefore, it is critical to elucidate the underlying mechanism upstream MEG3 to regulate breast cancer metastasis. We employed RT-qPCR and Western blot to examine expression level of miR-506, DNMT1, SP1, SP3 and MEG3. Besides, methylation-specific PCR was used to determine the methylation level of MEG3 promoter. Wound healing assay and transwell invasion assay were utilized to measure migration and invasion ability of breast cancer cells, respectively. SP was upregulated while miR-506 and MEG3 were downregulated in breast tumor tissue compared to adjacent normal breast tissues. In addition, we found that miR-506 regulated DNMT1 expression in an SP1/SP3-dependent manner, which reduced methylation level of MEG3 promoter and upregulated MEG3 expression. SP3 knockdown or miR-506 mimic suppressed migration and invasion of MCF-7 and MDA-MB-231 cells whereas overexpression of SP3 compromised miR-506-inhibited migration and invasion. Our data reveal a novel axis of miR-506/SP3/SP1/DNMT1/MEG3 in regulating migration and invasion of breast cancer cell lines, which provide rationales for developing effective therapies to treating metastatic breast cancers. 相似文献
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Chen JC Chen Y Wu JM Su YH Tai KF Tseng SH 《Cancer immunology, immunotherapy : CII》2006,55(7):873-883
Purpose: We investigated granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-12 (IL-12) infused into the injection
site of irradiated tumor vaccine (TV) as therapy for gliomas. Methods: Rats with subcutaneous RT-2 gliomas were treated with irradiated TV and/or subcutaneous infusion of GM-CSF and/or IL-12
via osmotic minipump 5 days after tumor-cell inoculation. Cytotoxic T lymphocyte (CTL) and natural killer (NK) cell activity
were analyzed to investigate immune responses. Rats with intracerebral gliomas were treated with irradiated TV and infused
GM-CSF/IL-12 3 days after tumor-cell inoculation. Tumor growth rates and animal survival were followed. Survivors were re-challenged
with wild-type RT-2 cells subcutaneously or intracerebrally to study long-term anti-tumor immunity. Results: Rats with subcutaneous gliomas treated with GM-CSF and IL-12 or TV plus GM-CSF or IL-12 did not have increased survival
rate (P>0.2), but did have prolonged survival time (P<0.05); in contrast, rats treated with TV plus GM-CSF/IL-12 had increased survival rate (P<0.05) and prolonged survival time (P<0.05) compared with controls. These treatment strategies showed enhanced CTL and NK cell activities. Rats with intra-cerebral
gliomas treated with TV plus GM-CSF/IL-12 did not have increased survival rate (P=0.11), but did have prolonged survival time (P<0.0001). Survivors in each group were re-challenged with wild-type RT-2 cells, and all had long-term survival. Conclusions: Irradiated TV plus continuous localized infusion of GM-CSF/IL-12 may induce a tumor-specific anti-tumor immune response
on established subcutaneous or intra-cerebral gliomas, and such a treatment strategy deserves consideration as adjuvant treatment
for glioma. 相似文献
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