Evidence map›Paper›PMID 37652480›Full record

ArticleIn vivo (Athens, Greece)

Therapeutic Efficacy of Temsirolimus in a Patient-derived Model of Metastatic Fibrolamellar Hepatocellular Carcinoma.

Jennifer L Leiting, Matthew C Hernandez, John R Bergquist, Jennifer A Yonkus, Amro M Abdelrahman, Michael S Torbenson, Nguyen H Tran, Thorvardur R Halfdanarson, Rondell P Graham, Rory L Smoot and 1 more

Open access · diamondAbstract read
In one paragraph

Article in In vivo (Athens, Greece). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.6field-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

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Review
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 3 institutions in 1 country.

Jennifer L LeitingDepartment of Surgery, Mayo Clinic, Rochester, MN, U.S.A.
Matthew C HernandezDepartment of Surgery, Mayo Clinic, Rochester, MN, U.S.A.
John R BergquistDepartment of Surgery, Mayo Clinic, Rochester, MN, U.S.A.
Jennifer A YonkusDepartment of Surgery, Mayo Clinic, Rochester, MN, U.S.A.
Amro M AbdelrahmanDepartment of Surgery, Mayo Clinic, Rochester, MN, U.S.A.
Michael S TorbensonDepartment of Medical Oncology, Mayo Clinic, Rochester, MN, U.S.A.
Nguyen H TranDepartment of Medical Oncology, Mayo Clinic, Rochester, MN, U.S.A.
Thorvardur R HalfdanarsonDepartment of Medical Oncology, Mayo Clinic, Rochester, MN, U.S.A.
Rondell P GrahamDepartment of Pathology, Mayo Clinic, Rochester, MN, U.S.A.
Rory L SmootDepartment of Surgery, Mayo Clinic, Rochester, MN, U.S.A.
Mark J TrutyDepartment of Surgery, Mayo Clinic, Rochester, MN, U.S.A.; truty.mark@mayo.edu.
Mayo Clinic in Arizona · USMayo Clinic · USMayo Clinic in Florida · US

Funding

Working to Eliminate Care Disparities in Liver Cancer in Southeast Asian Americans: Transportation and Other Social Determinants of Health.K23MD017217 · NIMHD · MAYO CLINIC ROCHESTER · PI Nguyen H Tran · 2022 to 2026
$818k
NIMHD NIH HHS K23 MD017217
6 · The paper itself

Abstract

BACKGROUND/

aimFibrolamellar hepatocellular carcinoma (FLHCC) is a rare tumor presenting in younger patients without chronic liver disease. Up to 80-100% develop recurrent disease, necessitating additional surgery or systemic treatment. Systemic options and pre-clinical treatment studies are lacking. We previously described patient-derived xenograft (PDX) development, allowing for pre-clinical studies. Herein, we develop FLHCC PDX models and utilize these to define tumor characteristics and determine the efficacy of systemic agents. MATERIALS AND

methodsPrimary and lymph node metastatic tumor tissues were obtained at the time of FLHCC resection in two patients. Tumor lysates were screened for protein upregulation. Cell lines were generated from metastatic and primary tumor tissue. The viability of the cell lines was assessed after treatment with temsirolimus, gemcitabine/oxaliplatin, and FOLFIRINOX. Two PDX models were developed from metastatic tissue. For in vivo studies, tumor-bearing mice were treated with temsirolimus, FOLFIRINOX, and Gemcitabine/oxaliplatin.

resultsPDX models were successfully generated from metastatic FLHCC, which closely recapitulated the original tumor. Upregulation of mTOR was seen in metastatic tissue compared to primary tumors. Cell lines from metastatic tissue demonstrated significant sensitivity to temsirolimus. In vivo testing of PDX models demonstrated a significant response to single-agent temsirolimus with minimal toxicity.

conclusionHerein, we demonstrate the feasibility of developing PDX models that closely recapitulate FLHCC. Upregulation of mTOR was seen in metastatic tissue compared to primary tissue. The efficacy of mTOR inhibition with temsirolimus treatment suggests that the upregulation of the mTOR pathway may be a significant mechanism for growth in metastatic lesions and a potential target for therapeutics.

Indexed as

Carcinoma, HepatocellularLiver NeoplasmsPancreatic NeoplasmsAnimalsAntineoplastic Combined Chemotherapy ProtocolsHumansMiceOxaliplatinSirolimusTOR Serine-Threonine KinasesOxaliplatinSirolimustemsirolimusTOR Serine-Threonine KinasesFibrolamellar hepatocellular carcinomapatient-derived xenografttemsirolimus

Identifiers

PMID37652480
PMCPMC10500502
OpenAlexW4386337283

What OpenQuestion holds

Textmetadata
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.