Evidence map›Paper›PMID 33436039›Full record

ArticleJournal of experimental & clinical cancer research : CR2021

A novel humanized Frizzled-7-targeting antibody enhances antitumor effects of Bevacizumab against triple-negative breast cancer via blocking Wnt/β-catenin signaling pathway.

Wei Xie, Huijie Zhao, Fengxian Wang, Yiyun Wang, Yuan He, Tong Wang, Kunchi Zhang, Hao Yang, Zhaoli Zhou, Haibin Shi and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
–field-weighted citation impact
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

25 citing papers in PubMed.

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  10. Synthesis of the scFv fragment of anti-Frizzled-7 antibody and evaluation of its effects on triple-negative breast cancer in vitro study.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024
    Article
  11. Review
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  19. Article
  20. Wnt Signaling in the Breast: From Development to Disease.Frontiers in cell and developmental biology · 2022
    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

12 authors.

Wei XieShanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, 279 Zhouzhu Highway, Pudong New Area, Shanghai, China. xiew@sumhs.edu.cn.
Huijie ZhaoShanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, 279 Zhouzhu Highway, Pudong New Area, Shanghai, China.
Fengxian WangShanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, 279 Zhouzhu Highway, Pudong New Area, Shanghai, China.
Yiyun WangShanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, 279 Zhouzhu Highway, Pudong New Area, Shanghai, China.
Yuan HeDepartment of Basic Medicine, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 211198, People's Republic of China.
Tong WangShanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, 279 Zhouzhu Highway, Pudong New Area, Shanghai, China.
Kunchi ZhangShanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, 279 Zhouzhu Highway, Pudong New Area, Shanghai, China.
Hao YangShanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, 279 Zhouzhu Highway, Pudong New Area, Shanghai, China.
Zhaoli ZhouShanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, 279 Zhouzhu Highway, Pudong New Area, Shanghai, China.
Haibin ShiShanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, 279 Zhouzhu Highway, Pudong New Area, Shanghai, China.
Jin WangSchool of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, People's Republic of China. wangj@sumhs.edu.cn.
Gang HuangShanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, 279 Zhouzhu Highway, Pudong New Area, Shanghai, China. huanggang@sumhs.edu.cn.

Funding

"Chen Guang" project supported by Shanghai Municipal Education Commission and Shanghai Education Development Foundation 18CG72Construction project of Shanghai Key Laboratory of Molecular Imaging 18DZ2260400National Natural Science Foundation of China NSFC81703401National Natural Science Foundation of China NSFC81801833National Natural Science Foundation of China NSFC81830052
6 · The paper itself

Abstract

backgroundAnti-angiogenic therapy has been widely applied to the clinical treatment of malignant tumors. However, the efficacy of such treatments has been called into question, especially in triple-negative breast cancer (TNBC). Bevacizumab, the first anti-angiogenic agent approved by FDA, actually increases invasive and metastatic properties of TNBC cells, resulting from the activation of Wnt/β-catenin signaling in response to hypoxia. As a critical receptor of Wnt/β-catenin signaling, Frizzled-7 (Fzd7) is aberrantly expressed in TNBC, indicating Fzd7 a potential target for developing drugs to be combined with anti-angiogenic agents.

methodsHybridoma technique and antibody humanization technique were utilized to generate a Fzd7-targeting antibody (SHH002-hu1). Biolayer interferometry (BLI) assay and near infrared (NIR) imaging were conducted to detect the affinity and targeting ability of SHH002-hu1. Next, whether SHH002-hu1 could suppress the invasion and migration of TNBC cells induced by Bevacizumab were validated, and the underlying molecular mechanisms were elucidated by luciferase reporter and western blot assays. The nude-mice transplanted TNBC models were established to assess the anti-TNBC activities of SHH002-hu1 when combined with Bevacizumab. Then, the effects on putative TNBC stem-like cells and Wnt/β-catenin signaling were evaluated by immunofluorescence (IF). Further, the tumor-initiating and self-renew capacity of TNBC cells were studied by secondary nude mouse xenograft model and sphere formation assay. In addition, the effects of SHH002-hu1 on the adaptation of TNBC cells to hypoxia were evaluated by the detection of vasculogenic mimicry (VM) and hypoxia-inducible factor-1α (HIF-1α) transcriptional activity.

resultsThe novel humanized antibody targeting Fzd7 (SHH002-hu1) exhibited extremely high affinity with Fzd7, and specifically targeted to Fzd7

conclusionSHH002-hu1 significantly enhances the anti-TNBC capacity of Bevacizumab, and shows the potential of preventing TNBC recurrence, suggesting SHH002-hu1 a good candidate for the synergistic therapy together with Bevacizumab.

Indexed as

AnimalsAntineoplastic Agents, ImmunologicalBevacizumabCell Line, TumorCricetulusFemaleFrizzled ReceptorsHumansMiceMice, NudeTriple Negative Breast NeoplasmsWnt Signaling PathwayXenograft Model Antitumor AssaysAntineoplastic Agents, ImmunologicalBevacizumabFrizzled ReceptorsFZD7 protein, humanAnti-angiogenesisAnti-Fzd7 antibodyHypoxiaTNBCWnt/β-catenin pathway

Identifiers

PMID33436039
PMCPMC7802198

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Registered trials

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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.