Evidence map›Paper›PMID 31584613›Full record

ArticleCarcinogenesis2020

Phospho-valproic acid (MDC-1112) reduces pancreatic cancer growth in patient-derived tumor xenografts and KPC mice: enhanced efficacy when combined with gemcitabine.

Dingyuan Luo, Matthew G Digiovanni, Ran Wei, Joseph F Lacomb, Jennie L Williams, Basil Rigas, Gerardo G Mackenzie

Open access · greenAbstract read
In one paragraph

Article in Carcinogenesis, 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
0.7field-weighted citation impact, top 26% 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, 7 citations in OpenAlex.

  1. Pooled it
  2. Article
  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

7 authors at 4 institutions in 2 countries.

Dingyuan LuoDepartment of Nutrition, University of California, Davis, One Shields Ave, Davis, CA, USA.
Matthew G DigiovanniDepartment of Nutrition, University of California, Davis, One Shields Ave, Davis, CA, USA.
Ran WeiDepartment of Nutrition, University of California, Davis, One Shields Ave, Davis, CA, USA.
Joseph F LacombDepartments of Family, Population and Preventive Medicine, Stony Brook, NY, USA.
Jennie L WilliamsDepartments of Family, Population and Preventive Medicine, Stony Brook, NY, USA.
Basil RigasMedicine, Stony Brook University, Stony Brook, NY, USA.
Gerardo G MackenzieDepartment of Nutrition, University of California, Davis, One Shields Ave, Davis, CA, USA.
Stony Brook Medicine · USStony Brook University · USSun Yat-sen University · CNUniversity of California, Davis · US

Funding

Staff InvestigatorsP30CA093373 · NCI · UNIVERSITY OF CALIFORNIA DAVIS · PI Gina M Dayton · 2002 to 2026
$84.9M
NCI NIH HHS P30 CA093373
6 · The paper itself

Abstract

New chemotherapeutic agents are needed for pancreatic cancer (PC). We have previously shown that phospho-valproic acid (MDC-1112) is effective in cell-line xenografts of PC. Here, we explored whether MDC-1112 is effective in additional clinically relevant animal models of PC and whether MDC-1112 enhances the anticancer effect of clinically used chemotherapeutic agents. MDC-1112 alone strongly reduced patient-derived pancreatic tumor xenograft growth, and extended survival of LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx1-Cre (KPC) mice. In both models, MDC-1112 inhibited STAT3 activation and its downstream signals, including Bcl-xL and cyclin D1. In human PC cell lines, P-V enhanced the growth inhibitory effect of gemcitabine (GEM), Abraxane and 5-FU, but not that of irinotecan. Normal human pancreatic epithelial cells were more resistant to the cytotoxic effects of MDC-1112/GEM combination. Furthermore, MDC-1112 enhanced GEM's effect on colony formation, apoptosis, cell migration, and cell invasion. In vivo, MDC-1112 and GEM, given alone, reduced patient-derived pancreatic tumor xenograft growth by 58% and 87%, respectively; whereas MDC-1112/GEM combination reduced tumor growth by 94%, inducing tumor stasis. In conclusion, MDC-1112 should be further explored as a potential agent to be used in combination with GEM for treating PC.

Indexed as

Abnormalities, MultipleAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisCell Line, TumorCell ProliferationDeoxycytidineDisease Models, AnimalGemcitabineHumansKeratoconusMiceOrganophosphatesPancreatic NeoplasmsSignal TransductionValproic AcidDeoxycytidineGemcitabineMDC-1112OrganophosphatesValproic Acid

Identifiers

PMID31584613
PMCPMC7951062
OpenAlexW2977581043

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.