Evidence map›Paper›PMID 24901052›Full record

ArticleCell death & disease2014

Rapamycin-enhanced mitomycin C-induced apoptotic death is mediated through the S6K1-Bad-Bak pathway in peritoneal carcinomatosis.

X Song, A-K Dilly, S-Y Kim, H A Choudry, Y J Lee

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

Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.7field-weighted citation impact, top 30% 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

9 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. mTORC Inhibitors as Broad-Spectrum Therapeutics for Age-Related Diseases.International journal of molecular sciences · 2018
    Review
  8. Article
  9. Article
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

5 authors at 1 institution in 1 country.

X SongDepartment of Surgery, University of Pittsburgh Cancer Institute, School of Medicine, Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15213, USA.
A-K DillyDepartment of Surgery, University of Pittsburgh Cancer Institute, School of Medicine, Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15213, USA.
S-Y KimDepartment of Surgery, University of Pittsburgh Cancer Institute, School of Medicine, Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15213, USA.
H A ChoudryDepartment of Surgery, University of Pittsburgh Cancer Institute, School of Medicine, Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Y J Lee1] Department of Surgery, University of Pittsburgh Cancer Institute, School of Medicine, Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15213, USA [2] Department of Pharmacology & Chemical Biology, University of Pittsburgh Cancer Institute, School of Medicine, Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15213, USA.
UPMC Hillman Cancer Center · US

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Jessie Nedrow · 1988 to 2026
$158.0M
Multimodality approach to hepatic colorectal metastasesR01CA140554 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BARTLETT, DAVID L, LEE, YONG J · 2010 to 2014
$1.6M
NCI NIH HHS CA140554NCI NIH HHS P30 CA047904NCI NIH HHS P30CA047904NCI NIH HHS R01 CA140554
6 · The paper itself

Abstract

Peritoneal carcinomatosis (PC) is the most common secondary cancerous disease, and more effective novel regimens are needed. In this study, we identified a novel combination treatment for PC, chemotherapeutic agent mitomycin C in combination with mTOR (mammalian target of rapamycin) inhibitor rapamycin. We observed that the combination of mitomycin C and rapamycin induced synergistic cytotoxicity and apoptosis, which was mediated through an increase in caspase activation. The combination of mitomycin C and rapamycin inactivated p70 S6 ribosomal kinase (S6K1) and dephosphorylated Bad, leading to dissociation of Bcl-xL from Bak, which resulted in Bak oligomerization, mitochondria dysfunction and cytochrome c release. PF-4708671, a S6K1-specific inhibitor, enhanced the combination treatment-induced apoptosis, whereas S6K1 E389 DeltaCT-HA (S6K1 active form) dramatically decreased the induction of apoptosis. In addition, the combination treatment significantly inhibited LS174T intraperitoneal tumor growth in vivo. This study provides a preclinical rationale for apoptosis induction linked with the mTOR pathway through a combination of chemotherapeutic agents and mTOR inhibitor, and will support this combinatorial strategy to PC patients.

Indexed as

AdenocarcinomaAnimalsAntibiotics, AntineoplasticApoptosisbcl-2 Homologous Antagonist-Killer Proteinbcl-Associated Death ProteinCell Line, TumorHumansMiceMice, NudeMitomycinPeritoneal NeoplasmsRibosomal Protein S6 Kinases, 70-kDaSirolimusAntibiotics, AntineoplasticBAD protein, humanBAK1 protein, humanbcl-2 Homologous Antagonist-Killer Proteinbcl-Associated Death ProteinMitomycinribosomal protein S6 kinase, 70kD, polypeptide 1Ribosomal Protein S6 Kinases, 70-kDaSirolimus

Identifiers

PMID24901052
PMCPMC4607229
OpenAlexW2034691444

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

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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.