Evidence map›Paper›PMID 37462741›Full record

ArticleAnalytical chemistry2023

Evaluating the Pharmacokinetics and Pharmacodynamics of Chemotherapeutics within a Spatial SILAC-Labeled Spheroid Model System.

Nicole C Beller, Yijia Wang, Amanda B Hummon

Open access · greenAbstract read
In one paragraph

Article in Analytical chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.7field-weighted citation impact, top 36% 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

6 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Mass Spectrometry-Based Applications of Spheroids in Cancer Biology.Annual review of analytical chemistry (Palo Alto, Calif.) · 2025
    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

3 authors at 1 institution in 1 country.

Nicole C BellerDepartment of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio 43210, United States.ORCID 0000-0003-4036-5648
Yijia WangDepartment of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio 43210, United States.
Amanda B HummonDepartment of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio 43210, United States.ORCID 0000-0002-1969-9013
The Ohio State University · US

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Daniel G. Stover · 1985 to 2026
$132.3M
Spatial SILAC: Examining the Proteome in 3D Cell CulturesR01GM110406 · NIGMS · UNIVERSITY OF NOTRE DAME · PI HUMMON, AMANDA B. · 2014 to 2022
$3.0M
15 Tesla Bruker solariX FTICR MSS10OD018507 · OD · OHIO STATE UNIVERSITY · PI WYSOCKI, VICKI H. · 2014 to 2014
$2.0M
Acquisition of a Next Generation Orbitrap MSS10OD018056 · OD · OHIO STATE UNIVERSITY · PI FREITAS, MICHAEL A. · 2014 to 2014
$573k
NCI NIH HHS P30 CA016058NIGMS NIH HHS R01 GM110406NIH HHS S10 OD018056NIH HHS S10 OD018507
6 · The paper itself

Abstract

Tumors have considerable cellular heterogeneity that is impossible to explore with simple cell cultures. Spheroid cultures contain pathophysiological and chemical gradients similar to in vivo tumors and show complex responses to therapeutics, similar to a tumor. Using pulsed isotopic labels, we demonstrate the pronounced differential response of the proteome to the drug Regorafenib, a multikinase inhibitor, in HCT 116 spheroids. Regorafenib treatment of outer spheroids inhibits proteins involved in critical pathways such as mTOR signaling, extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) signaling, and colorectal cancer metastasis signaling, resulting in decreased proliferation and cellular apoptosis. By contrast, analysis of the treated core cells shows upregulation of MAPK1 and KRAS, possibly implicating drug resistance within these late apoptotic cells. Thus, pulsed isotopic labeling enables evaluation of the distinct proteomic responses for cells residing in the different chemical microenvironments of the spheroid. This platform promises great utility in assisting researchers' predictions of pharmacodynamic therapeutic responses within complex tumors.

Indexed as

Antineoplastic AgentsNeoplasmsCell Line, TumorHumansPhenylurea CompoundsProteomicsPyridinesSignal TransductionSpheroids, CellularTumor MicroenvironmentAntineoplastic AgentsPhenylurea CompoundsPyridinesregorafenib

Identifiers

PMID37462741
PMCPMC10676637
OpenAlexW4384627043

What Socratic holds

Textmetadata
LicenceTDM
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.