Evidence map›Paper›PMID 42856641›Full record

ArticlebioRxiv : the preprint server for biology2026

Epithelial to mesenchymal transition and M2 macrophages drive aggressiveness in murine and human sarcomatoid urothelial carcinoma.

Yujiro Hayashi, Roy Elias, Eugene Douglass, Akinaru Yamamoto, Matthew Schuler, Mingxiao Feng, Ekatherina Y Batourina, Anne E Geller, Woonyoung Choi, Gabriela Colocho and 20 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

30 authors.

Yujiro HayashiGreenberg Bladder Cancer Institute, Johns Hopkins University.
Roy EliasGreenberg Bladder Cancer Institute, Johns Hopkins University.
Eugene DouglassCollege of Pharmacy, University of Georgia.
Akinaru YamamotoGreenberg Bladder Cancer Institute, Johns Hopkins University.
Matthew SchulerGreenberg Bladder Cancer Institute, Johns Hopkins University.
Mingxiao FengGreenberg Bladder Cancer Institute, Johns Hopkins University.
Ekatherina Y BatourinaDepartment of Pathology, Columbia University.
Anne E GellerDepartment of Urology, Johns Hopkins University.
Woonyoung ChoiGreenberg Bladder Cancer Institute, Johns Hopkins University.
Gabriela ColochoGreenberg Bladder Cancer Institute, Johns Hopkins University.
Alyssa ArbuisoGreenberg Bladder Cancer Institute, Johns Hopkins University.
Samuel JinGreenberg Bladder Cancer Institute, Johns Hopkins University.
Adam K AragakiGreenberg Bladder Cancer Institute, Johns Hopkins University.
Charles RulandGreenberg Bladder Cancer Institute, Johns Hopkins University.
Stanley RapieyGreenberg Bladder Cancer Institute, Johns Hopkins University.
Jean Hoffman-CensitsGreenberg Bladder Cancer Institute, Johns Hopkins University.
Max KatesGreenberg Bladder Cancer Institute, Johns Hopkins University.
Sunil H PatelGreenberg Bladder Cancer Institute, Johns Hopkins University.
Nirmish SinglaGreenberg Bladder Cancer Institute, Johns Hopkins University.
Armine SmithGreenberg Bladder Cancer Institute, Johns Hopkins University.
Stephanie RussellGreenberg Bladder Cancer Institute, Johns Hopkins University.
Huili LiDepartment of Pathology, Johns Hopkins University.
Joshua I WarrickDepartment of Pathology, Yale University.
Ezra BarabanDepartment of Pathology, Johns Hopkins University.
Karin AllenspachCollege of Veterinary Medicine, University of Georgia.
Cathy L MendelsohnDepartment of Pathology, Columbia University.ORCID 0000-0002-4026-4073
Andres MatosoDepartment of Pathology, Johns Hopkins University.
Noah M HahnGreenberg Bladder Cancer Institute, Johns Hopkins University.
David J McConkeyGreenberg Bladder Cancer Institute, Johns Hopkins University.
Burles A JohnsonGreenberg Bladder Cancer Institute, Johns Hopkins University.

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI WILLIAM George NELSON · 1985 to 2026
$208.6M
Phase 1/2 Study of Modern Immunotherapy in BCG-Relapsing Urothelial Carcinoma of the Bladder - (ADAPT-BLADDER)R01CA235681 · NCI · JOHNS HOPKINS UNIVERSITY · PI HAHN, NOAH M · 2019 to 2024
$3.2M
NCI NIH HHS P30 CA006973NCI NIH HHS R01 CA235681
6 · The paper itself

Abstract

Patients with majority variant subtype histology including sarcomatoid urothelial carcinoma (SUC) have poor outcomes and limited treatment options, and there are few preclinical resources to investigate rare histologic subtypes. We developed three novel variant subtype histology bladder cancer (BC) cell lines by finding that basal BC tumor cells derived from mice treated with N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) were initially not competent to grow in immune competent mice, but then acquired tumorigenicity following passaging ("recycling") in mice lacking mature B and T cells. Three genitourinary oncology pathologists identified BBN966 as SUC, BBN964 as a hybrid between SUC and squamous, and BBN975 as squamous, and each had unique growth characteristics. Using a publicly available dataset and our spatial transcriptomics analysis of a cohort of human tumors with mixed SUC and UC as comparators, we found that consistent with human SUC, BBN966 lack expression of basal and luminal genes. Consistent with human SUC and spatial transcriptomics analysis of canine SUC, BBN966 had the highest epithelial to mesenchymal transition (EMT) upregulation, and all three recycled tumor cells had increased EMT pathway expression in recycled tumor cells. Moreover, increased expression of genes upregulated in all three recycled tumor cells associated with worse overall survival in patients with muscle invasive UC. Similar to human SUC, BBN966 tumors had higher proportion of M2 macrophage gene expression. Finally, we found in the largest cohort of PD-L1 IHC to date that 20 of 38 (52.6%) human SUC had CPS ≥ 50, which was driven mostly by tumor proportion score. Consistent with this, we found anti-PD1 immune checkpoint inhibitor (ICI) significantly inhibited BBN966 tumor growth, while the hybrid BBN964 tumors had mixed response to ICI. Thus, the murine BBN966 tumors exhibited similarities to human SUC, and can be used to examine novel therapies for translation into future SUC clinical studies.

Identifiers

PMID42856641
PMCPMC13648735

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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.