Evidence map›Paper›PMID 22531721›Full record

ArticleBritish journal of cancer2012

Downregulation of membrane complement inhibitors CD55 and CD59 by siRNA sensitises uterine serous carcinoma overexpressing Her2/neu to complement and antibody-dependent cell cytotoxicity in vitro: implications for trastuzumab-based immunotherapy.

S Bellone, D Roque, E Cocco, S Gasparrini, I Bortolomai, N Buza, M Abu-Khalaf, D-A Silasi, E Ratner, M Azodi and 4 more

Open access · hybridAbstract read
In one paragraph

Article in British journal of cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
4.5field-weighted citation impact, top 6% 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

24 citing papers in PubMed, 58 citations in OpenAlex.

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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

14 authors at 2 institutions in 2 countries.

S BelloneDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
D Roque
E Cocco
S Gasparrini
I Bortolomai
N Buza
M Abu-Khalaf
D-A Silasi
E Ratner
M Azodi
P E Schwartz
T J Rutherford
S Pecorelli
A D Santin
Yale University · USUniversity of Brescia · IT

Funding

Yale Pathology Tissue Services Shared ResourceP30CA016359 · NCI · YALE UNIVERSITY · PI DAVID L RIMM · 1985 to 2026
$85.0M
CPE Peptide-Based Nanoparticles for the Diagnosis and Therapy of Chemotherapy ResR01CA154460 · NCI · YALE UNIVERSITY · PI SANTIN, ALESSANDRO D · 2011 to 2015
$1.7M
Treatment of Chemotherapy-Resistant Human Ovarian Cancer by Administration of CPER01CA122728 · NCI · YALE UNIVERSITY · PI SANTIN, ALESSANDRO D · 2008 to 2011
$1.4M
NCI NIH HHS CA-16359NCI NIH HHS P30 CA016359NCI NIH HHS R01 CA122728NCI NIH HHS R01 CA122728-01A4NCI NIH HHS R01 CA154460NCI NIH HHS R01 CA154460-01A1
6 · The paper itself

Abstract

backgroundWe evaluated the expression of CD46, CD55 and CD59 membrane-bound complement-regulatory proteins (mCRPs) in primary uterine serous carcinoma (USC) and the ability of small interfering RNA (siRNA) against these mCRPs to sensitise USC to complement-dependent cytotoxicity (CDC) and antibody (trastuzumab)-dependent cellular cytotoxicity (ADCC) in vitro.

methodsMembrane-bound complement-regulatory proteins expression was evaluated using real-time PCR (RT-PCR) and flow cytometry, whereas Her2/neu expression and c-erbB2 gene amplification were assessed using immunohistochemistry, flow cytometry and fluorescent in-situ hybridisation. The biological effect of siRNA-mediated knockdown of mCRPs on HER2/neu-overexpressing USC cell lines was evaluated in CDC and ADCC 4-h chromium-release assays.

resultsHigh expression of mCRPs was found in USC cell lines when compared with normal endometrial cells (P<0.05). RT-PCR and FACS analyses demonstrated that anti-mCRP siRNAs were effective in reducing CD46, CD55 and CD59 expression on USC (P<0.05). Baseline complement-dependent cytotoxicity (CDC) against USC cell lines was low (mean ± s.e.m.=6.8 ± 0.9%) but significantly increased upon CD55 and CD59 knockdown (11.6 ± 0.8% and 10.7 ± 0.9%, respectively, P<0.05). Importantly, in the absence of complement, both CD55 and CD59, but not CD46, knockdowns significantly augmented ADCC against USC overexpressing Her2/neu.

conclusionUterine serous carcinoma express high levels of the mCRPs CD46, CD55 and CD59. Small interfering RNA inhibition of CD55 and CD59, but not CD46, sensitises USC to both CDC and ADCC in vitro, and if specifically targeted to tumour cells, may significantly increase trastuzumab-mediated therapeutic effect in vivo.

Indexed as

Antibody-Dependent Cell CytotoxicityAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedCD55 AntigensCD59 AntigensComplement ActivationCystadenocarcinoma, SerousCytotoxicity, ImmunologicDown-RegulationErb-b2 Receptor Tyrosine KinasesFemaleFlow CytometryHumansIn Situ Hybridization, FluorescenceAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedCD55 AntigensCD59 AntigensERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesMembrane Cofactor ProteinRNA, Small InterferingTrastuzumab

Identifiers

PMID22531721
PMCPMC3341945
OpenAlexW1965205267

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.