Evidence map›Paper›PMID 23879689›Full record

ArticleInternational journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group2013

A role for the copper transporter Ctr1 in the synergistic interaction between hyperthermia and cisplatin treatment.

Chelsea D Landon, Sarah E Benjamin, Kathleen A Ashcraft, Mark W Dewhirst

Open access · greenAbstract read
In one paragraph

Article in International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

10 citing papers in PubMed, 29 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

4 authors at 1 institution in 1 country.

Chelsea D LandonDepartment of Pathology, Duke University, Durham, NC, USA.
Sarah E Benjamin
Kathleen A Ashcraft
Mark W Dewhirst
Duke University · US

Funding

TISSUEP01CA042745 · NCI · DUKE UNIVERSITY · PI DEWHIRST, MARK WESLEY · 1987 to 2009
$28.6M
The Use of Hyperthermia and Copper Chelation to Overcome Cisplatin ResistanceF31AT006644 · NCCIH · DUKE UNIVERSITY · PI LANDON, CHELSEA DAWN · 2011 to 2013
$68k
NCCIH NIH HHS 1F31 AT006644-01NCCIH NIH HHS F31 AT006644NCI NIH HHS CA42745NCI NIH HHS P01 CA042745
6 · The paper itself

Abstract

purposeHyperthermia enhances cytotoxic effects of chemotherapeutic agents such as cisplatin. However, the underlying molecular mechanisms remain unclear. We hypothesised that hyperthermia increases cisplatin accumulation and efficacy by modulating function of copper transport protein 1 (Ctr1), a major regulator of cellular cisplatin uptake. We examined the significance of Ctr1 in the synergistic interaction between hyperthermia and cisplatin. We assessed the importance of cisplatin- and hyperthermia-induced Ctr1 multimerisation in sensitising cells to cisplatin cytotoxicity. MATERIALS AND

methodsCtr1 protein levels and cisplatin sensitivities were assessed in bladder cancer cell lines with immunoblotting and clonogenic survival assays. Using Myc-tagged-Ctr1 HEK293 cells, we assessed the effect of hyperthermia on Ctr1 multimerisation with immunoblotting. The effect of hyperthermia on cisplatin sensitivity and accumulation was assessed in wild-type (WT) and Ctr1 knockout (Ctr1-/-) mouse embryonic fibroblasts (MEFs) with clonogenic assays and inductively coupled plasma-mass spectrometry (ICP-MS).

resultsIncreased Ctr1 protein expression was observed for the most cisplatin-sensitive bladder cancer cell lines and MEFs. Heat-induced increase in Ctr1 multimerisation with cisplatin was observed in Myc-tagged Ctr1 cells. Hyperthermia enhanced cisplatin-mediated cytotoxicity in WT more than Ctr1-/- cells (dose modifying factors 1.75 versus 1.4, respectively). WT cells accumulated more platinum versus Ctr1-/- cells; this was further increased by hyperthermia in WT cells.

conclusionsHyperthermia enhanced cisplatin uptake and cytotoxicity in WT cells. Heat increased Ctr1 activity by increasing multimerisation, enhancing drug cytotoxicity. Furthermore, Ctr1 protein profiles of bladder tumours, as well as other tumour types, may predict their response to cisplatin and overall efficacy of treatment.

Indexed as

Hyperthermia, InducedAnimalsAntineoplastic AgentsCation Transport ProteinsCell LineCell Line, TumorCell SurvivalCisplatinCopper Transporter 1FibroblastsHEK293 CellsHumansMiceRNA, MessengerUrinary Bladder NeoplasmsAntineoplastic AgentsCation Transport ProteinsCisplatinCopper Transporter 1RNA, Messenger

Identifiers

PMID23879689
PMCPMC3895488
OpenAlexW1978606749

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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.