Evidence map›Paper›PMID 28933554›Full record

ArticleMolecular pharmaceutics2017

Rational Targeting of Cellular Cholesterol in Diffuse Large B-Cell Lymphoma (DLBCL) Enabled by Functional Lipoprotein Nanoparticles: A Therapeutic Strategy Dependent on Cell of Origin.

Jonathan S Rink, Shuo Yang, Osman Cen, Tim Taxter, Kaylin M McMahon, Sol Misener, Amir Behdad, Richard Longnecker, Leo I Gordon, C Shad Thaxton

Open access · greenAbstract read
In one paragraph

Article in Molecular pharmaceutics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
1.2field-weighted citation impact, top 24% 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

27 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Metabolic Reprogramming and Potential Therapeutic Targets in Lymphoma.International journal of molecular sciences · 2023
    Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Btk Inhibitors: A Medicinal Chemistry and Drug Delivery Perspective.International journal of molecular sciences · 2021
    Review
  20. 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

10 authors at 1 institution in 1 country.

Jonathan S RinkNorthwestern University, Feinberg School of Medicine , Department of Urology, Chicago, Illinois 60611, United States.
Shuo YangNorthwestern University, Feinberg School of Medicine , Division of Hematology/Oncology, Department of Medicine, Chicago, Illinois 60611, United States.
Osman CenNorthwestern University, Feinberg School of Medicine , Division of Hematology/Oncology, Department of Medicine, Chicago, Illinois 60611, United States.
Tim TaxterNorthwestern University, Feinberg School of Medicine , Department of Pathology, Chicago, Illinois 60611, United States.
Kaylin M McMahonNorthwestern University, Feinberg School of Medicine , Department of Urology, Chicago, Illinois 60611, United States.
Sol MisenerNorthwestern University, Feinberg School of Medicine , Department of Urology, Chicago, Illinois 60611, United States.
Amir BehdadNorthwestern University, Feinberg School of Medicine , Department of Pathology, Chicago, Illinois 60611, United States.
Richard LongneckerNorthwestern University, Feinberg School of Medicine , Department of Microbiology and Immunology, Chicago, Illinois 60611, United States.
Leo I GordonNorthwestern University, Feinberg School of Medicine , Division of Hematology/Oncology, Department of Medicine, Chicago, Illinois 60611, United States.
C Shad ThaxtonNorthwestern University, Feinberg School of Medicine , Department of Urology, Chicago, Illinois 60611, United States.ORCID 0000-0002-4765-6213
Northwestern University · US

Funding

Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LEONIDAS C. PLATANIAS · 1993 to 2026
$153.9M
Theranostic Magnetic Nanostructures for the Molecular Imaging of CancerU54CA151880 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI MIRKIN, CHAD A. · 2010 to 2014
$11.5M
In Vivo Model of Epstein-Barr Virus LatencyR01CA073507 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LONGNECKER, RICHARD M · 1997 to 2018
$6.1M
Novel Vehicles for Targeted Cardiovascular RepairR01HL116577 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI KIBBE, MELINA RAE, STUPP, SAMUEL I · 2013 to 2016
$4.3M
Vascular Surgery Scientist Training ProgramT32HL094293 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI ESKANDARI, MARK K · 2009 to 2023
$4.0M
High Density Lipoprotein Nanoparticles for siRNA DeliveryR01CA167041 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI THAXTON, COLBY SHAD · 2012 to 2016
$1.6M
Cancer Nanotechnology Training ProgramT32CA186897 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI WOLOSCHAK, GAYLE E. · 2015 to 2019
$1.2M
Howard Hughes Medical InstituteNCI NIH HHS L30 CA162042NCI NIH HHS P30 CA060553NCI NIH HHS R01 CA073507NCI NIH HHS R01 CA167041NCI NIH HHS T32 CA186897NCI NIH HHS U54 CA151880NHLBI NIH HHS R01 HL116577NHLBI NIH HHS T32 HL094293
6 · The paper itself

Abstract

Cancer cells have altered metabolism and, in some cases, an increased demand for cholesterol. It is important to identify novel, rational treatments based on biology, and cellular cholesterol metabolism as a potential target for cancer is an innovative approach. Toward this end, we focused on diffuse large B-cell lymphoma (DLBCL) as a model because there is differential cholesterol biosynthesis driven by B-cell receptor (BCR) signaling in germinal center (GC) versus activated B-cell (ABC) DLBCL. To specifically target cellular cholesterol homeostasis, we employed high-density lipoprotein-like nanoparticles (HDL NP) that can generally reduce cellular cholesterol by targeting and blocking cholesterol uptake through the high-affinity HDL receptor, scavenger receptor type B-1 (SCARB1). As we previously reported, GC DLBCL are exquisitely sensitive to HDL NP as monotherapy, while ABC DLBCL are less sensitive. Herein, we report that enhanced BCR signaling and resultant de novo cholesterol synthesis in ABC DLBCL drastically reduces the ability of HDL NPs to reduce cellular cholesterol and induce cell death. Therefore, we combined HDL NP with the BCR signaling inhibitor ibrutinib and the SYK inhibitor R406. By targeting both cellular cholesterol uptake and BCR-associated de novo cholesterol synthesis, we achieved cellular cholesterol reduction and induced apoptosis in otherwise resistant ABC DLBCL cell lines. These results in lymphoma demonstrate that reduction of cellular cholesterol is a powerful mechanism to induce apoptosis. Cells rich in cholesterol require HDL NP therapy to reduce uptake and molecularly targeted agents that inhibit upstream pathways that stimulate de novo cholesterol synthesis, thus, providing a new paradigm for rationally targeting cholesterol metabolism as therapy for cancer.

Indexed as

Antineoplastic AgentsApoptosisCholesterolHumansLipoproteins, HDLLymphoma, Large B-Cell, DiffuseNanoparticlesReceptors, Antigen, B-CellReceptors, LipoproteinScavenger Receptors, Class BSignal TransductionAntineoplastic AgentsCholesterolhigh density lipoprotein receptorsLipoproteins, HDLReceptors, Antigen, B-CellReceptors, LipoproteinSCARB1 protein, humanScavenger Receptors, Class BB-cell receptor signalingcholesterolhigh-density lipoproteinslymphomananoparticles

Identifiers

PMID28933554
PMCPMC6004607
OpenAlexW2759664130

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.