Evidence map›Paper›PMID 37796299›Full record

ArticleCancer immunology, immunotherapy : CII2023

An optimized protocol for the generation and monitoring of conditional orthotopic lung cancer in the KP mouse model using an adeno-associated virus vector compatible with biosafety level 1.

Haibin Deng, Huixiang Ge, Christelle Dubey, Tereza Losmanova, Michaela Medová, Georgia Konstantinidou, Seyran Mathilde Mutlu, Fabienne Esther Birrer, Tess Melinda Brodie, Deborah Stroka and 4 more

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

Article in Cancer immunology, immunotherapy : CII, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.6field-weighted citation impact, top 14% 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

4 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. 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

14 authors at 3 institutions in 2 countries.

Haibin DengDepartment of General Thoracic Surgery, Inselspital, Bern University Hospital, University of Bern, Murtenstrasse 28, 3008, Bern, Switzerland.
Huixiang GeDepartment of General Thoracic Surgery, Inselspital, Bern University Hospital, University of Bern, Murtenstrasse 28, 3008, Bern, Switzerland.
Christelle DubeyDepartment of General Thoracic Surgery, Inselspital, Bern University Hospital, University of Bern, Murtenstrasse 28, 3008, Bern, Switzerland.
Tereza LosmanovaInstitute of Pathology, University of Bern, Bern, Switzerland.
Michaela MedováDepartment for BioMedical Research, University of Bern, Bern, Switzerland.
Georgia KonstantinidouInstitute of Pharmacology, University of Bern, Bern, Switzerland.
Seyran Mathilde MutluDepartment for BioMedical Research, University of Bern, Bern, Switzerland.
Fabienne Esther BirrerDepartment for BioMedical Research, University of Bern, Bern, Switzerland.
Tess Melinda BrodieDepartment for BioMedical Research, University of Bern, Bern, Switzerland.
Deborah StrokaDepartment for BioMedical Research, University of Bern, Bern, Switzerland.
Wenxiang WangThoracic Surgery Department 2, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China.
Ren-Wang PengDepartment of General Thoracic Surgery, Inselspital, Bern University Hospital, University of Bern, Murtenstrasse 28, 3008, Bern, Switzerland. renwang.peng@insel.ch.
Patrick DornDepartment of General Thoracic Surgery, Inselspital, Bern University Hospital, University of Bern, Murtenstrasse 28, 3008, Bern, Switzerland. patrick.dorn@insel.ch.
Thomas Michael MartiDepartment of General Thoracic Surgery, Inselspital, Bern University Hospital, University of Bern, Murtenstrasse 28, 3008, Bern, Switzerland. thomas.marti@insel.ch.
University Hospital of Bern · CHUniversity of Bern · CHHunan Cancer Hospital · CN

Funding

Chinese Scholarship Council HDSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung 310030_192648Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung 310030_212418Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung 310030_212766-1Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung 316030_183501Swiss Cancer Research Foundation KFS-5405-08-2021-R
6 · The paper itself

Abstract

backgroundThe inducible Kras/p53 lung adenocarcinoma mouse model, which faithfully recapitulates human disease, is routinely initiated by the intratracheal instillation of a virus-based Cre recombinase delivery system. Handling virus-based delivery systems requires elevated biosafety levels, e.g., biosafety level 2 (BSL-2). However, in experimental animal research facilities, following exposure to viral vectors in a BSL-2 environment, rodents may not be reclassified to BSL-1 according to standard practice, preventing access to small animal micro-computed tomography (micro-CT) scanners that are typically housed in general access areas such as BSL-1 rooms. Therefore, our goal was to adapt the protocol so that the Cre-induced KP mouse model could be handled under BSL-1 conditions during the entire procedure.

resultsThe Kras-Lox-STOP-Lox-G12D/p53 flox/flox (KP)-based lung adenocarcinoma mouse model was activated by intratracheal instillation of either an adenoviral-based or a gutless, adeno-associated viral-based Cre delivery system. Tumor growth was monitored over time by micro-CT. We have successfully substituted the virus-based Cre delivery system with a commercially available, gutless, adeno-associated, Cre-expressing vector that allows the KP mouse model to be handled and imaged in a BSL-1 facility. By optimizing the anesthesia protocol and switching to a microscope-guided vector instillation procedure, productivity was increased and procedure-related complications were significantly reduced. In addition, repeated micro-CT analysis of individual animals allowed us to monitor tumor growth longitudinally, dramatically reducing the number of animals required per experiment. Finally, we documented the evolution of tumor volume for different doses, which revealed that individual tumor nodules induced by low-titer AAV-Cre transductions can be monitored over time by micro-CT.

conclusionModifications to the anesthesia and instillation protocols increased the productivity of the original KP protocol. In addition, the switch to a gutless, adeno-associated, Cre-expressing vector allowed longitudinal monitoring of tumor growth under BSL-1 conditions, significantly reducing the number of animals required for an experiment, in line with the 3R principles.

Indexed as

Adenocarcinoma of LungLung NeoplasmsAnimalsContainment of BiohazardsDependovirusDisease Models, AnimalGenetic VectorsHumansMiceProto-Oncogene Proteins p21(ras)Tumor Suppressor Protein p53X-Ray MicrotomographyProto-Oncogene Proteins p21(ras)Tumor Suppressor Protein p53AAV vectorBSL-1Cre-expressing vectorIntratracheal instillationLung adenocarcinomaMouse model

Identifiers

PMID37796299
PMCPMC10700219
OpenAlexW4387357609

What Socratic 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 Socratic graph.