Abstract:
BACKGROUND:Advanced cancer and chemotherapy are both associated with immune system suppression. We initiated a clinical trial in patients receiving chemotherapy for metastatic colorectal cancer to determine if administration of GM-CSF in this setting was immunostimulatory. METHODS:Between June, 2003 and January, 2007, 20 patients were enrolled in a clinical trial (NCT00257322) in which they received 500 ug GM-CSF daily for 4 days starting 24 hours after each chemotherapy cycle. There were no toxicities or adverse events reported. Blood was obtained before chemotherapy/GM-CSF administration and 24 hours following the final dose of GM-CSF and evaluated for circulating dendritic cells and adaptive immune cellular subsets by flow cytometry. Peripheral blood mononuclear cell (PBMC) expression of γ-interferon and T-bet transcription factor (Tbx21) by quantitative real-time PCR was performed as a measure of Th1 adaptive cellular immunity. Pre- and post-treatment (i.e., chemotherapy and GM-CSF) samples were evaluable for 16 patients, ranging from 1 to 5 cycles (median 3 cycles, 6 biologic sample time points). Dendritic cells were defined as lineage (-) and MHC class II high (+). RESULTS:73% of patients had significant increases in circulating dendritic cells of ~3x for the overall group (5.8% to 13.6%, p = 0.02) and ~5x excluding non-responders (3.2% to 14.5%, p < 0.001). This effect was sustained over multiple cycles for approximately half of the responders, but tachyphylaxis over subsequent chemotherapy cycles was noted for the remainder. Treatment also led to a significant reduction in the proportion of circulating regulatory T-cells (Treg; p = 0.0042). PBMC Tbx21 levels declined by 75% following each chemotherapy cycle despite administration of GM-CSF (p = 0.02). PBMC γ-interferon expression, however was unchanged. CONCLUSIONS:This clinical trial confirms the suppressive effects of chemotherapy on Th1 cellular immunity in patients with metastatic colorectal cancer but demonstrates that mid-cycle administration of GM-CSF can significantly increase the proportion of circulating dendritic cells. As the role of dendritic cells in anti-tumor immunity becomes better defined, GM-CSF administration may provide a non-toxic intervention to augment this arm of the immune system for cancer patients receiving cytotoxic therapy. TRIAL REGISTRATION:ClinicalTrials.gov: NCT00257322.
journal_name
Cancer Cell Intjournal_title
Cancer cell internationalauthors
Martinez M,Ono N,Planutiene M,Planutis K,Nelson EL,Holcombe RFdoi
10.1186/1475-2867-12-2subject
Has Abstractpub_date
2012-01-23 00:00:00pages
2issue
1issn
1475-2867pii
1475-2867-12-2journal_volume
12pub_type
杂志文章abstract::An area of research that has been recently gaining attention is the relationship between cancer stem cell (CSC) biology and chemo-resistance in colon cancer patients. It is well recognized that tumor initiation, growth, invasion and metastasis are promoted by CSCs. An important reason for the widespread interest in th...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-015-0163-7
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abstract:Background:Colorectal cancer (CRC) is one of the most common malignant tumors in the world. Siah E3 ubiquitin protein ligase 1 (Siah1) has been identified as a tumor suppressor gene and plays an important role in the development of malignant tumors. However, the potential role and molecular mechanism of Siah1 in the de...
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abstract::[This retracts the article DOI: 10.1186/s12935-015-0237-6.]. ...
journal_title:Cancer cell international
pub_type: 撤回出版物
doi:10.1186/s12935-016-0359-5
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journal_title:Cancer cell international
pub_type: 杂志文章
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pub_type: 杂志文章
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abstract:BACKGROUND:This last decade, a lot of emphasis has been placed on developing new cancer cell culture models, closer to in vivo condition, in order to test new drugs and therapies. In the case of colorectal cancer, the use of patient biopsies to seed 3D primary cultures and mimic tumor initiation necessitates the use of...
journal_title:Cancer cell international
pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Cancer cell international
pub_type: 杂志文章
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journal_title:Cancer cell international
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Cancer cell international
pub_type: 杂志文章
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更新日期:2018-11-13 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
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更新日期:2019-02-28 00:00:00
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pub_type: 杂志文章
doi:10.1186/s12935-018-0716-7
更新日期:2018-12-22 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2018-08-13 00:00:00
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pub_type: 杂志文章
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/1475-2867-12-26
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pub_type: 杂志文章
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更新日期:2018-12-27 00:00:00
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pub_type: 杂志文章
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更新日期:2011-10-31 00:00:00
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pub_type: 杂志文章
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更新日期:2018-12-19 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
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更新日期:2019-03-20 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-014-0133-5
更新日期:2014-11-30 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
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更新日期:2021-01-12 00:00:00
abstract:BACKGROUND:BRAF inhibitors are effective anticancer agents in BRAF-mutated melanomas. By contrast, evidences about sensitivity of thyroid carcinomas to BRAF inhibition are conflicting and it has been proposed that BRAF V600E thyroid carcinoma cells are less sensitive to BRAF inhibitors due to activation of parallel sig...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-017-0457-z
更新日期:2017-10-04 00:00:00
abstract:Background:Breast cancer is the leading cause of oncological mortality among women. Efficient detection of cancer cells in an early stage and potent therapeutic agents targeting metastatic tumors are highly needed to improve survival rates. Emerging evidence indicates that lncRNAs (long noncoding RNAs) are critical reg...
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更新日期:2018-09-18 00:00:00
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更新日期:2020-05-24 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-01690-1
更新日期:2021-01-11 00:00:00