Evidence map›Paper›PMID 33671932›Full record

ArticleCancers2021

Differential Effects of Trp53 Alterations in Murine Colorectal Cancer.

Alexander M Betzler, Lahiri K Nanduri, Barbara Hissa, Linda Blickensdörfer, Michael H Muders, Janine Roy, Moritz Jesinghaus, Katja Steiger, Wilko Weichert, Matthias Kloor and 7 more

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

Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.8field-weighted citation impact, top 31% 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

5 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
  2. Review
  3. A hitchhiker's guide to cancer models.Trends in biotechnology · 2022
    Review
  4. Article
  5. Article
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

17 authors at 7 institutions in 2 countries.

Alexander M BetzlerDepartment of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany.
Lahiri K NanduriDepartment of Gastrointestinal, Thoracic and Vascular Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany.ORCID 0000-0002-0258-6055
Barbara HissaDepartment of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany.
Linda BlickensdörferDepartment of General, Gastrointestinal and Transplant Surgery, Ruprecht-Karls-Universität Heidelberg, 69120 Heidelberg, Germany.
Michael H MudersInstitute of Pathology, University of Bonn Medical Center, 53127 Bonn, Germany.
Janine RoyDepartment of Bioinformatics, Biotechnology Center, Technische Universität Dresden, 01307 Dresden, Germany.
Moritz JesinghausInstitute of Pathology, Technische Universität München, 81675 München, Germany.
Katja SteigerInstitute of Pathology, Technische Universität München, 81675 München, Germany.ORCID 0000-0002-7269-5433
Wilko WeichertInstitute of Pathology, Technische Universität München, 81675 München, Germany.
Matthias KloorDepartment of Applied Tumor Biology, Institute of Pathology, Ruprecht-Karls-Universität Heidelberg, 69120 Heidelberg, Germany.
Barbara KlinkInstitute of Clinical Genetics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany.
Michael SchroederDepartment of Bioinformatics, Biotechnology Center, Technische Universität Dresden, 01307 Dresden, Germany.
Massimiliano MazzoneLaboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium.
Jürgen WeitzDepartment of Gastrointestinal, Thoracic and Vascular Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany.
Christoph ReissfelderDepartment of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany.ORCID 0000-0003-4591-1046
Nuh N RahbariDepartment of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany.
Sebastian SchölchDepartment of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany.ORCID 0000-0003-0012-3177
Heidelberg University · DETechnical University of Munich · DEUniversity Hospital Carl Gustav Carus · DEGerman Cancer Research Center · DETechnische Universität Dresden · DEUniversity of Bonn · DEVIB-KU Leuven Center for Cancer Biology · BE

Funding

Deutsche Forschungsgemeinschaft WE 3548/4-1Roland Ernst Stiftung RES 1/14
6 · The paper itself

Abstract

backgroundColorectal cancer (CRC) development is a multi-step process resulting in the accumulation of genetic alterations. Despite its high incidence, there are currently no mouse models that accurately recapitulate this process and mimic sporadic CRC. We aimed to develop and characterize a genetically engineered mouse model (GEMM) of Apc/Kras/Trp53 mutant CRC, the most frequent genetic subtype of CRC.

methodsTumors were induced in mice with conditional mutations or knockouts in Apc, Kras, and Trp53 by a segmental adeno-cre viral infection, monitored via colonoscopy and characterized on multiple levels via immunohistochemistry and next-generation sequencing.

resultsThe model accurately recapitulates human colorectal carcinogenesis clinically, histologically and genetically. The Trp53 R172H hotspot mutation leads to significantly increased metastatic capacity. The effects of Trp53 alterations, as well as the response to treatment of this model, are similar to human CRC. Exome sequencing revealed spontaneous protein-modifying alterations in multiple CRC-related genes and oncogenic pathways, resulting in a genetic landscape resembling human CRC.

conclusionsThis model realistically mimics human CRC in many aspects, allows new insights into the role of TP53 in CRC, enables highly predictive preclinical studies and demonstrates the value of GEMMs in current translational cancer research and drug development.

Indexed as

adenovirusApccolorectal cancerGEMMgenetically engineered mouse modelKrasmetastasispreclinical studiesTP53Trp53

Identifiers

PMID33671932
PMCPMC7919037
OpenAlexW3132528123

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.