Evidence map›Paper›PMID 35087225›Full record

ArticleCommunications biology2022

Differential toxicity to murine small and large intestinal epithelium induced by oncology drugs.

Jake M Bieber, Laura E Sanman, Xiaoxiao Sun, Heinz Hammerlindl, Feng Bao, Maike A Roth, Megan L Koleske, Liusheng Huang, Fran Aweeka, Lani F Wu and 1 more

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

Article in Communications biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.8field-weighted citation impact, top 30% 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

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Review
  2. Article
  3. 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

11 authors at 1 institution in 1 country.

Jake M BieberDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, 94158, USA.ORCID http://orcid.org/0000-0002-3993-6004
Laura E SanmanDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, 94158, USA.ORCID http://orcid.org/0000-0002-5453-8063
Xiaoxiao SunDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, 94158, USA.
Heinz HammerlindlDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, 94158, USA.
Feng BaoDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, 94158, USA.ORCID http://orcid.org/0000-0002-5721-9551
Maike A RothDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, 94158, USA.
Megan L KoleskeDepartment of Bioengineering and Therapeutics, University of California, San Francisco, San Francisco, CA, 94158, USA.ORCID http://orcid.org/0000-0002-9826-6442
Liusheng HuangDrug Research Unit, Department of Clinical Pharmacology, University of California, San Francisco, San Francisco, CA, 94158, USA.
Fran AweekaDrug Research Unit, Department of Clinical Pharmacology, University of California, San Francisco, San Francisco, CA, 94158, USA.
Lani F WuDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, 94158, USA. lani.wu@ucsf.edu.ORCID http://orcid.org/0000-0002-0052-7537
Steven J AltschulerDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, 94158, USA. steven.altschuler@ucsf.edu.ORCID http://orcid.org/0000-0001-9142-0796
University of California, San Francisco · US

Funding

PHARMACEUTICAL SCIENCES AND PHARMACOGENOMICST32GM007175 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AHITUV, NADAV, KROETZ, DEANNA L · 1985 to 2021
$7.1M
Maximizing the predictive power of high-throughput, microscopy-based phenotypic screensR01CA184984 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WU, LANI F · 2014 to 2025
$4.7M
Systems-level role of GSK3 in colonic epithelium homeostasis and drug resistanceR01GM112690 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ALTSCHULER, STEVEN J · 2015 to 2018
$1.3M
NCI NIH HHS R01 CA184984NIGMS NIH HHS R01 GM112690NIGMS NIH HHS T32 GM007175
6 · The paper itself

Abstract

Gastrointestinal toxicity is a major concern in the development of drugs. Here, we establish the ability to use murine small and large intestine-derived monolayers to screen drugs for toxicity. As a proof-of-concept, we applied this system to assess gastrointestinal toxicity of ~50 clinically used oncology drugs, encompassing diverse mechanisms of action. Nearly all tested drugs had a deleterious effect on the gut, with increased sensitivity in the small intestine. The identification of differential toxicity between the small and large intestine enabled us to pinpoint differences in drug uptake (antifolates), drug metabolism (cyclophosphamide) and cell signaling (EGFR inhibitors) across the gut. These results highlight an under-appreciated distinction between small and large intestine toxicity and suggest distinct tissue properties important for modulating drug-induced gastrointestinal toxicity. The ability to accurately predict where and how drugs affect the murine gut will accelerate preclinical drug development.

Indexed as

AnimalsAntineoplastic AgentsCell SurvivalEpithelial CellsIntestinal DiseasesIntestinal MucosaIntestinesMiceMice, Inbred C57BLAntineoplastic Agents

Identifiers

PMID35087225
PMCPMC8795448
OpenAlexW4210523244

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.