Evidence map›Paper›PMID 26405195›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016

Impaired Synthesis of Stromal Components in Response to Minnelide Improves Vascular Function, Drug Delivery, and Survival in Pancreatic Cancer.

Sulagna Banerjee, Shrey Modi, Olivia McGinn, Xianda Zhao, Vikas Dudeja, Sundaram Ramakrishnan, Ashok K Saluja

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed, 1 pooled it
15.0field-weighted citation impact, top 1% 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

66 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.

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6 more citing papers are in PubMed but not listed here.

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

7 authors at 1 institution in 1 country.

Sulagna BanerjeeDivision of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, Minnesota.
Shrey ModiDivision of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, Minnesota.
Olivia McGinnDivision of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, Minnesota.
Xianda ZhaoDivision of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, Minnesota.
Vikas DudejaDivision of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, Minnesota.
Sundaram RamakrishnanDepartment of Pharmacology, University of Minnesota, Minneapolis, Minnesota.
Ashok K SalujaDivision of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, Minnesota. asaluja@umn.edu.
University of Minnesota · US

Funding

The Inhibition of HSP70 Induces Apoptosis in Pancreatic Cancer CellsR01CA124723 · NCI · UNIVERSITY OF MINNESOTA · PI GILBOA, ELI, RAMAKRISHNAN, SUNDARAM · 2007 to 2022
$4.5M
Triptolide Augments Death Receptor Mediated Apoptosis in Pancreatic CancerR01CA170946 · NCI · UNIVERSITY OF MINNESOTA · PI SALUJA, ASHOK K · 2012 to 2016
$2.4M
Functional Significance of CD133 in Pancreatic CancerR01CA184274 · NCI · UNIVERSITY OF MINNESOTA · PI BANERJEE, SULAGNA · 2014 to 2018
$1.6M
NCI NIH HHS CA124723NCI NIH HHS R01 CA124723NCI NIH HHS R01 CA170946NCI NIH HHS R01-CA170946NCI NIH HHS R01 CA184274NCI NIH HHS R01-CA184274
6 · The paper itself

Abstract

purposePancreatic cancer stromal microenvironment is considered to be the major reason for failure of conventional and targeted therapy for this disease. The desmoplastic stroma, comprising mainly collagen and glycosaminoglycans like hyaluronan (HA), is responsible for compression of vasculature in the tumor resulting in impaired drug delivery and poor prognosis. Minnelide, a water-soluble prodrug of triptolide currently in phase I clinical trial, has been very effective in multiple animal models of pancreatic cancer. However, whether Minnelide will have efficacious delivery into the tumor despite the desmoplastic stroma has not been evaluated before. EXPERIMENT

designPatient tumor-derived xenografts (PDX) and spontaneous pancreatic cancer mice were treated with 0.42 and 0.21 mg/kg body weight for 30 days. Stromal components were determined by IHC and ELISA-based assays. Vascular functionality and drug delivery to the tumor were assessed following treatment with Minnelide.

resultOur current study shows that treatment with Minnelide resulted in reduction of ECM components like HA and collagen in the pancreatic cancer stroma of both the spontaneous KPC mice as well as in patient tumor xenografts. Furthermore, treatment with Minnelide improved functional vasculature in the tumors resulting in four times more functional vessels in the treated animals compared with untreated animals. Consistent with this observation, Minnelide also resulted in increased drug delivery into the tumor compared with untreated animals. Along with this, Minnelide also decreased viability of the stromal cells along with the tumor cells in pancreatic adenocarcinoma.

conclusionsIn conclusion, these results are extremely promising as they indicate that Minnelide, along with having anticancer effects is also able to deplete stroma in pancreatic tumors, which makes it an effective therapy for pancreatic cancer.

Indexed as

AdenocarcinomaAnimalsAntineoplastic AgentsCell Line, TumorCell SurvivalDiterpenesDrug Delivery SystemsEpoxy CompoundsHumansMiceMice, Inbred NODMice, SCIDOrganophosphatesPancreatic NeoplasmsPhenanthrenesStromal Cells14-O-phosphonooxymethyltriptolide disodium saltAntineoplastic AgentsDiterpenesEpoxy CompoundsOrganophosphatesPhenanthrenestriptolide

Identifiers

PMID26405195
PMCPMC4716007
OpenAlexW2192209315

What OpenQuestion holds

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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.