Evidence map›Paper›PMID 29027990›Full record

ArticleCell death and differentiation2018

IL6 blockade potentiates the anti-tumor effects of γ-secretase inhibitors in Notch3-expressing breast cancer.

Dong Wang, Jiahui Xu, Bingjie Liu, Xueyan He, Lei Zhou, Xin Hu, Feng Qiao, Anli Zhang, Xiaojun Xu, Huafeng Zhang and 4 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death and differentiation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
1.8field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 54 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Review
  6. Article
  7. Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Targeting Breast Cancer Stem Cells.International journal of biological sciences · 2023
    Review
  17. Review
  18. Article
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 8 institutions in 2 countries.

Dong WangHefei National Laboratory for Physical Sciences at the Microscale, School of Life Science, University of Science & Technology of China, Hefei, Anhui, China.
Jiahui XuHefei National Laboratory for Physical Sciences at the Microscale, School of Life Science, University of Science & Technology of China, Hefei, Anhui, China.
Bingjie LiuHefei National Laboratory for Physical Sciences at the Microscale, School of Life Science, University of Science & Technology of China, Hefei, Anhui, China.
Xueyan HeKey Laboratory of Breast Cancer in Shanghai, Cancer Institute, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Lei ZhouHefei National Laboratory for Physical Sciences at the Microscale, School of Life Science, University of Science & Technology of China, Hefei, Anhui, China.
Xin HuKey Laboratory of Breast Cancer in Shanghai, Cancer Institute, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Feng QiaoKey Laboratory of Breast Cancer in Shanghai, Cancer Institute, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Anli ZhangDepartment of Pathology, Anhui Provincial Hospital, Southern District, Hefei, Anhui, China.
Xiaojun XuThe Department of Breast Surgery, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China.
Huafeng ZhangHefei National Laboratory for Physical Sciences at the Microscale, School of Life Science, University of Science & Technology of China, Hefei, Anhui, China.
Max S WichaUniversity of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
Lixing ZhangKey Laboratory of Breast Cancer in Shanghai, Cancer Institute, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Zhi-Ming ShaoKey Laboratory of Breast Cancer in Shanghai, Cancer Institute, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Suling LiuKey Laboratory of Breast Cancer in Shanghai, Cancer Institute, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Shanghai Cancer Institute · CNFudan University Shanghai Cancer Center · CNHefei National Center for Physical Sciences at Nanoscale · CNAnhui Medical University · CNAnhui Provincial Hospital · CNShanghai Medical College of Fudan University · CNUniversity of Michigan–Ann Arbor · USXiamen University · CN

Funding

Targeting breast cancer stem cellsR35CA197585 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WICHA, MAX S. · 2016 to 2022
$6.4M
NCI NIH HHS R35 CA197585
6 · The paper itself

Abstract

Notch pathways have important roles in carcinogenesis including pathways involving the Notch1 and Notch2 oncogenes. Pan-Notch inhibitors, such as gamma secretase inhibitors (GSIs), have been used in the clinical trials, but the outcomes of these trials have been insufficient and have yielded unclear. In the present study, we demonstrated that GSIs, such as MK-0752 and RO4929097, inhibit breast tumor growth, but increase the breast cancer stem cell (BCSC) population in Notch3-expressing breast cancer cells, in a process that is coupled with IL6 induction and is blocked by the IL6R antagonist Tocilizumab (TCZ). IL6 induction results from inhibition of Notch3-Hey2 signaling through MK-0752. Furthermore, HIF1α upregulates Notch3 expression via direct binding to the Notch3 promoter and subsequently downregulates BCSCs by decreasing the IL6 levels in Notch3-expressing breast cancer cells. Utilizing both breast cancer cell line xenografts and patient-derived xenografts (PDX), we showed that the combination of MK-0752 and Tocilizumab significantly decreases BCSCs and inhibits tumor growth and thus might serve as a novel therapeutic strategy for treating women with Notch3-expressing breast cancers.

Indexed as

Amyloid Precursor Protein SecretasesAnimalsAntibodies, Monoclonal, HumanizedBenzazepinesBenzene DerivativesBreast NeoplasmsCell ProliferationEnzyme InhibitorsFemaleFluorocarbonsHumansInterleukin-6Mammary Neoplasms, ExperimentalMiceMice, NudeNeoplastic Stem Cells2,2-dimethyl-N-(6-oxo-6,7-dihydro-5H-dibenzo(b,d)azepin-7-yl)-N'-(2,2,3,3,3-pentafluoropropyl)malonamide3-(4-((4-chlorophenyl)sulfonyl)-4-(2,5-difluorophenyl)cyclohexyl)propanoic acidAmyloid Precursor Protein SecretasesAntibodies, Monoclonal, HumanizedBenzazepinesBenzene DerivativesEnzyme InhibitorsFluorocarbonsInterleukin-6NOTCH3 protein, humanPropionatesReceptor, Notch3Sulfonestocilizumab

Identifiers

PMID29027990
PMCPMC5762847
OpenAlexW2762543424

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.