Evidence map›Paper›PMID 35457006›Full record

ArticleInternational journal of molecular sciences2022

The Tumor Microenvironment Drives Intrahepatic Cholangiocarcinoma Progression.

Serena Mancarella, Grazia Serino, Sergio Coletta, Raffaele Armentano, Francesco Dituri, Francesco Ardito, Andrea Ruzzenente, Isabel Fabregat, Gianluigi Giannelli

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 2 pooled it
3.1field-weighted citation impact, top 8% 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

18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 15 citations in OpenAlex.

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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

9 authors at 4 institutions in 2 countries.

Serena MancarellaNational Institute of Gastroenterology “S. De Bellis”, IRCCS Research Hospital, 70013 Castellana Grotte, ItalyORCID 0000-0003-2692-1169
Grazia SerinoNational Institute of Gastroenterology “S. De Bellis”, IRCCS Research Hospital, 70013 Castellana Grotte, ItalyORCID 0000-0002-2971-0802
Sergio ColettaNational Institute of Gastroenterology “S. De Bellis”, IRCCS Research Hospital, 70013 Castellana Grotte, Italy
Raffaele ArmentanoNational Institute of Gastroenterology “S. De Bellis”, IRCCS Research Hospital, 70013 Castellana Grotte, ItalyORCID 0000-0003-1661-5504
Francesco DituriNational Institute of Gastroenterology “S. De Bellis”, IRCCS Research Hospital, 70013 Castellana Grotte, Italy
Francesco ArditoHepatobiliary Surgery Unit, Foundation "Policlinico Universitario A. Gemelli", IRCCS, Catholic University, 00168 Rome, Italy.
Andrea RuzzenenteDepartment of Surgery, General and Hepatobiliary Surgery, University Hospital G.B. Rossi, University and Hospital Trust of Verona, 37126 Verona, Italy.ORCID 0000-0001-6911-563X
Isabel FabregatOncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), CIBEREHD and University of Barcelona, 08908 L'Hospitalet de Llobregat, Spain.ORCID 0000-0003-0136-8440
Gianluigi GiannelliNational Institute of Gastroenterology “S. De Bellis”, IRCCS Research Hospital, 70013 Castellana Grotte, Italy
Gastroenterology Hospital "Saverio de Bellis" · ITAgostino Gemelli University Polyclinic · ITInstitut d'Investigació Biomédica de Bellvitge · ESUniversity of Verona · IT

Funding

Italian Association for Cancer Research 18737
6 · The paper itself

Abstract

Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive cancer with limited therapeutic options and short overall survival. iCCA is characterized by a strong desmoplastic reaction in the surrounding ecosystem that likely affects tumoral progression. Overexpression of the Notch pathway is implicated in iCCA development and progression. Our aim was to investigate the effectiveness of Crenigacestat, a selective inhibitor of NOTCH1 signaling, against the cross-talk between cancer cells and the surrounding ecosystem in an in vivo HuCCT1-xenograft model. In the present study, a transcriptomic analysis approach, validated by Western blotting and qRT-PCR on iCCA tumor masses treated with Crenigacestat, was used to study the molecular pathways responsive to drug treatment. Our results indicate that Crenigacestat significantly inhibited NOTCH1 and HES1, whereas tumor progression was not affected. In addition, the drug triggered a strong immune response and blocked neovascularization in the tumor ecosystem of the HuCCT1-xenograft model without affecting the occurrence of fibrotic reactions. Therefore, although these data need further investigation, our observations confirm that Crenigacestat selectively targets NOTCH1 and that the desmoplastic response in iCCA likely plays a key role in both drug effectiveness and tumor progression.

Indexed as

Bile Duct NeoplasmsCholangiocarcinomaBile Ducts, IntrahepaticEcosystemHumansTumor Microenvironmentgene expressionHuCCT1-xenograft mouse modelintrahepatic cholangiocarcinomamicroenvironmentNOTCH1

Identifiers

PMID35457006
PMCPMC9032805
OpenAlexW4223426049

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.