Evidence map›Paper›PMID 32029905›Full record

ArticleCancer gene therapy2020

Non-toxic fragment of botulinum neurotoxin type A and monomethyl auristatin E conjugate for targeted therapy for neuroendocrine tumors.

Jason Whitt, Won S Hong, Rahul R Telange, Chee Paul Lin, James Bibb, David J Beebe, Herbert Chen, Renata Jaskula-Sztul

Abstract read
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In one paragraph

Article in Cancer gene therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
0.3field-weighted citation impact, top 42% 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

3 citing papers in PubMed, 1 synthesis or guideline pooled it, 3 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. 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

8 authors at 2 institutions in 1 country.

Jason Whitt *Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA. jwhitt@uabmc.edu.
Won S Hong *Pathology and Laboratory Medicine and Biomedical Engineering, UW-Madison, Madison, WI, USA.
Rahul R TelangeDepartment of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
Chee Paul LinCenter for Clinical and Translational Science, University of Alabama at Birmingham, Birmingham, AL, USA.
James BibbDepartment of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
David J BeebePathology and Laboratory Medicine and Biomedical Engineering, UW-Madison, Madison, WI, USA.
Herbert ChenDepartment of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
Renata Jaskula-SztulDepartment of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
University of Alabama at Birmingham · USUniversity of Wisconsin–Madison · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Surgical resection is the only cure for neuroendocrine tumors (NETs). However, widespread metastases have already occured by the time of initial diagnosis in many cases making complete surgical removal impossible. We developed a recombinant heavy-chain receptor binding domain (rHCR) of botulinum neurotoxin type A that can specifically target synaptic vesicle 2 (SV2), a surface receptor abundantly expressed in multiple neuroendocrine tumors. Expression of neuroendocrine differentiation markers chromogranin A (CgA) and achaete-scute complex 1 (ASCL1) were signficantly reduced when treated with rHCR. rHCR conjugated to the antimitotic agent monomethyl auristatin E (MMAE) significantly suppressed proliferation of pancreatic carcinoid (BON) and medullary thyroid cancer cells (MZ) at concentrations of 500 and 300 nM respectively, while no growth suppression was observed in pulmonary fibroblasts and cortical neuron control cell lines. In vivo, rHCR-MMAE significantly reduced tumor volume in mouse xenografts with no observed adverse effects. These data suggest recombinant HCR (rHCR) of BoNT/A preferentially targets neuroendocrine cancer without the neurotoxicity of the full BoNT/A and that SV2 is a specific and promising target for delivering drugs to neuroendocrine tumors.

Indexed as

AnimalsApoptosisBotulinum Toxins, Type ACell Line, TumorCell ProliferationDisease Models, AnimalHumansMiceNeuroendocrine TumorsNeuromuscular AgentsOligopeptidesBotulinum Toxins, Type Amonomethyl auristatin ENeuromuscular AgentsOligopeptides

Identifiers

PMID32029905
OpenAlexW3004638974

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.