Evidence map›Paper›PMID 25735654›Full record

ArticleOral oncology2015

Combined TP53 mutation/3p loss correlates with decreased radiosensitivity and increased matrix-metalloproteinase activity in head and neck carcinoma.

Sharat C Raju, Samantha J Hauff, Aaron J Lemieux, Ryan K Orosco, Andrew M Gross, Linda T Nguyen, Elamprakash Savariar, William Moss, Michael Whitney, Ezra E Cohen and 5 more

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

Article in Oral oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.5field-weighted citation impact, top 10% 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

8 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Genetic analysis of radiation-specific biomarkers in sinonasal squamous cell carcinomas.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016
    Article
  8. 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

15 authors at 3 institutions in 1 country.

Sharat C RajuDivision of Head and Neck Surgery, University of California, San Diego, CA, USA.
Samantha J HauffDivision of Head and Neck Surgery, University of California, San Diego, CA, USA.
Aaron J LemieuxDivision of Head and Neck Surgery, University of California, San Diego, CA, USA.
Ryan K OroscoDivision of Head and Neck Surgery, University of California, San Diego, CA, USA.
Andrew M GrossBioinfomatics and Systems Biology, University of California, San Diego, CA, USA.
Linda T NguyenDivision of Head and Neck Surgery, University of California, San Diego, CA, USA.
Elamprakash SavariarDepartment of Pharmacology, University of California, San Diego, CA, USA.
William MossDivision of Head and Neck Surgery, University of California, San Diego, CA, USA.
Michael WhitneyDepartment of Pharmacology, University of California, San Diego, CA, USA.
Ezra E CohenMoores Cancer Center, San Diego, CA, USA.
Scott M LippmanMoores Cancer Center, San Diego, CA, USA.
Roger Y TsienDepartment of Pharmacology, University of California, San Diego, CA, USA; Howard Hughes Medical Institute, San Diego, CA, USA.
Trey IdekerBioinfomatics and Systems Biology, University of California, San Diego, CA, USA; Division of Medical Genetics, University of California, San Diego, CA, USA.
Sunil J AdvaniDepartment of Radiation Medicine and Applied Sciences, University of California, San Diego, CA, USA.
Quyen T NguyenDivision of Head and Neck Surgery, University of California, San Diego, CA, USA; Department of Pharmacology, University of California, San Diego, CA, USA; Moores Cancer Center, San Diego, CA, USA. Electronic address: q1nguyen@ucsd.edu.
University of California San Diego · USMoores Cancer CenterHoward Hughes Medical Institute · US

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIANE M SIMEONE · 1985 to 2026
$124.9M
SYNTHETIC SYSTEMSP50GM085764 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HASTY, JEFF M, IDEKER, TREY · 2010 to 2018
$23.3M
A Systems Approach to Mapping the DNA Damage ResponseR01ES014811 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IDEKER, TREY · 2005 to 2021
$8.6M
Injectable reporters to image tumors and guide resectionR01CA158448 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI NGUYEN, QUYEN · 2011 to 2015
$3.1M
OTOLARYNGOLOGY TRAINING IN IMMUN., VIROL. &MOLEC. BIOL.T32DC000028 · NIDCD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI RYAN, ALLEN F. · 1989 to 2020
$2.1M
Testing Fluorescently Labeled Probes for Nerve Imaging during SurgeryR01EB014929 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI NGUYEN, QUYEN · 2012 to 2016
$1.7M
San Diego Clinical and Translational Research InstituteTL1RR031979 · NCRR · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S · 2010 to 2011
$885k
NCI NIH HHS P30 CA023100NCI NIH HHS P30CA023100NCI NIH HHS R01 CA158448NCRR NIH HHS RR031979NCRR NIH HHS TL1 RR031979NIBIB NIH HHS R01 EB014929NIDCD NIH HHS T32 DC000028NIEHS NIH HHS ES014811NIEHS NIH HHS R01 ES014811NIGMS NIH HHS GM085764NIGMS NIH HHS P50 GM085764Wellcome Trust
6 · The paper itself

Abstract

objectivePatients with head and neck squamous cell carcinoma (HNSCC) containing TP53 mutation and 3p deletion ("double-hit") have poorer prognosis compared to patients with either event alone ("single-hit"). The etiology for worse clinical outcomes in patients with "double-hit" cancers is unclear. We compared radiosensitivity of cell lines containing both TP53 mutations and deletion of Fragile Histidine Triad (FHIT, the gene most commonly associated with 3p deletion) to "single-hit" lines with only TP53 mutation. We compared radiosensitivity in a "single-hit" cell line with TP53 mutation converted to "double-hit" using RNA interference targeting FHIT. Finally, we compared matrixmetalloproteinase-2/9 (MMP-2/9) activity, a previously-established biomarker for tumor aggressiveness, in xenograft tumors derived from these cell lines. MATERIALS/

methodsTP53 mutation and FHIT deletion profiles of HNSCC lines were established using Cancer Cell Line Encyclopedia (CCLE). We used RNA-interference to convert a "single-hit" cell line (SCC4) to "double-hit". Cultured cells were examined for radiosensitivity and cisplatin sensitivity. MMP-2/9 activity was evaluated in "double-hit" versus "single-hit" tumors using ratiometric activatable cell-penetrating peptide (RACPP) in tongue (n=17) and flank xenografts (n=4).

resultsRadiotherapy caused greater double-stranded DNA breaks in "single-hit" vs naturally occurring and engineered "double-hit" cells. In-vivo, "double-hit" xenografts demonstrated higher MMP-2/9 activity compared to "single-hit" xenografts (p<0.01). There was no difference in cisplatin sensitivity between the cell lines.

conclusionsTP53 mutation combined with FHIT deletion correlates with decreased radiosensitivity in HNC cell lines. Xenograft from "double-hit" cells exhibit increased MMP-2/9 activity. These findings may in part account for the worse clinical outcome seen in patients with HNSCC "double-hit" tumors.

Indexed as

Chromosome DeletionChromosomes, Human, Pair 3Genes, p53Acid Anhydride HydrolasesBis(5'-adenosyl)triphosphataseCarcinoma, Squamous CellCell Line, TumorHead and Neck NeoplasmsHumansMatrix MetalloproteinasesMutationNeoplasm ProteinsRadiation ToleranceAcid Anhydride HydrolasesBis(5'-adenosyl)triphosphataseMatrix MetalloproteinasesNeoplasm Proteins3p Deletion“double-hit”Double-stranded DNA breaksFHITHead and neck cancerMatrix metalloproteinasesRadiosensitivityRNA interference“single-hit”TP53 mutation

Identifiers

PMID25735654
PMCPMC4427339
OpenAlexW2060626309

What OpenQuestion holds

Textmetadata
LicenceTDM
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.