| Title |
A proof of principle clinical trial to determine whether conjugated linoleic acid modulates the lipogenic pathway in human breast cancer tissue
|
|---|---|
| Published in |
Breast Cancer Research and Treatment, February 2013
|
| DOI | 10.1007/s10549-013-2446-9 |
| Pubmed ID | |
| Authors |
Margit M. McGowan, Burton L. Eisenberg, Lionel D. Lewis, Heather M. Froehlich, Wendy A. Wells, Alan Eastman, Nancy B. Kuemmerle, Kari M. Rosenkrantz, Richard J. Barth, Gary N. Schwartz, Zhongze Li, Tor D. Tosteson, Bernard B. Beaulieu, William B. Kinlaw |
| Abstract |
Conjugated linoleic acid (CLA) is widely used as a "nutraceutical" for weight loss. CLA has anticancer effects in preclinical models, and we demonstrated in vitro that this can be attributed to the suppression of fatty acid (FA) synthesis. We tested the hypothesis that administration of CLA to breast cancer patients would inhibit expression of markers related to FA synthesis in tumor tissue, and that this would suppress tumor proliferation. Women with Stage I-III breast cancer were enrolled into an open label study and treated with CLA (1:1 mix of 9c,11t- and 10t,12c-CLA isomers, 7.5 g/d) for ≥ 10 days before surgery. Fasting plasma CLA concentrations measured pre- and post-CLA administration, and pre/post CLA tumor samples were examined by immunohistochemistry for Spot 14 (S14), a regulator of FA synthesis, FA synthase (FASN), an enzyme of FA synthesis, and lipoprotein lipase (LPL), the enzyme that allows FA uptake. Tumors were also analyzed for expression of Ki-67 and cleaved caspase 3. 24 women completed study treatment, and 23 tumors were evaluable for the primary endpoint. The median duration of CLA therapy was 12 days, and no significant toxicity was observed. S14 expression scores decreased (p = 0.003) after CLA administration. No significant change in FASN or LPL expression was observed. Ki-67 scores declined (p = 0.029), while cleaved caspase 3 staining was unaffected. Decrements in S14 or Ki-67 did not correlate with fasting plasma CLA concentrations at surgery. Breast tumor tissue expression of S14, but not FASN or LPL, was decreased after a short course of treatment with 7.5 g/day CLA. This was accompanied by reductions in the proliferation index. CLA consumption was well-tolerated and safe at this dose for up to 20 days. Overall, CLA may be a prototype compound to target fatty acid synthesis in breast cancers with a "lipogenic phenotype". |
Mendeley readers
The data shown below were compiled from readership statistics for 78 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Brazil | 1 | 1% |
| Unknown | 77 | 99% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 16 | 21% |
| Student > Bachelor | 14 | 18% |
| Student > Ph. D. Student | 10 | 13% |
| Researcher | 6 | 8% |
| Other | 4 | 5% |
| Other | 10 | 13% |
| Unknown | 18 | 23% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 15 | 19% |
| Agricultural and Biological Sciences | 13 | 17% |
| Biochemistry, Genetics and Molecular Biology | 8 | 10% |
| Nursing and Health Professions | 5 | 6% |
| Social Sciences | 3 | 4% |
| Other | 13 | 17% |
| Unknown | 21 | 27% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 August 2014.
All research outputs
#18,332,122
of 22,701,287 outputs
Outputs from Breast Cancer Research and Treatment
#3,682
of 4,619 outputs
Outputs of similar age
#145,657
of 191,516 outputs
Outputs of similar age from Breast Cancer Research and Treatment
#39
of 50 outputs
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