Evidence map›Paper›PMID 28880787›Full record

ArticleRadiology2018

Targeting STAT3 to Suppress Systemic Pro-Oncogenic Effects from Hepatic Radiofrequency Ablation.

Gaurav Kumar, S Nahum Goldberg, Svetlana Gourevitch, Tatyana Levchenko, Vladimir Torchilin, Eithan Galun, Muneeb Ahmed

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

Article in Radiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

29 citing papers in PubMed, 41 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Gaurav KumarFrom the Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, 1 Deaconess Rd, WCC 308-B, Boston, MA 02215 (G.K., S.N.G., M.A.); Division of Image-guided Therapy and Interventional Oncology, Department of Radiology (S.N.G.), and Goldyne Savad Institute of Gene Therapy (S.G., E.G.), Hadassah Hebrew University Hospital, Jerusalem, Israel; and Department of Pharmaceutical Sciences, Northeastern University, Boston, Mass (T.L., V.T.).
S Nahum GoldbergFrom the Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, 1 Deaconess Rd, WCC 308-B, Boston, MA 02215 (G.K., S.N.G., M.A.); Division of Image-guided Therapy and Interventional Oncology, Department of Radiology (S.N.G.), and Goldyne Savad Institute of Gene Therapy (S.G., E.G.), Hadassah Hebrew University Hospital, Jerusalem, Israel; and Department of Pharmaceutical Sciences, Northeastern University, Boston, Mass (T.L., V.T.).
Svetlana GourevitchFrom the Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, 1 Deaconess Rd, WCC 308-B, Boston, MA 02215 (G.K., S.N.G., M.A.); Division of Image-guided Therapy and Interventional Oncology, Department of Radiology (S.N.G.), and Goldyne Savad Institute of Gene Therapy (S.G., E.G.), Hadassah Hebrew University Hospital, Jerusalem, Israel; and Department of Pharmaceutical Sciences, Northeastern University, Boston, Mass (T.L., V.T.).
Tatyana LevchenkoFrom the Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, 1 Deaconess Rd, WCC 308-B, Boston, MA 02215 (G.K., S.N.G., M.A.); Division of Image-guided Therapy and Interventional Oncology, Department of Radiology (S.N.G.), and Goldyne Savad Institute of Gene Therapy (S.G., E.G.), Hadassah Hebrew University Hospital, Jerusalem, Israel; and Department of Pharmaceutical Sciences, Northeastern University, Boston, Mass (T.L., V.T.).
Vladimir TorchilinFrom the Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, 1 Deaconess Rd, WCC 308-B, Boston, MA 02215 (G.K., S.N.G., M.A.); Division of Image-guided Therapy and Interventional Oncology, Department of Radiology (S.N.G.), and Goldyne Savad Institute of Gene Therapy (S.G., E.G.), Hadassah Hebrew University Hospital, Jerusalem, Israel; and Department of Pharmaceutical Sciences, Northeastern University, Boston, Mass (T.L., V.T.).
Eithan GalunFrom the Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, 1 Deaconess Rd, WCC 308-B, Boston, MA 02215 (G.K., S.N.G., M.A.); Division of Image-guided Therapy and Interventional Oncology, Department of Radiology (S.N.G.), and Goldyne Savad Institute of Gene Therapy (S.G., E.G.), Hadassah Hebrew University Hospital, Jerusalem, Israel; and Department of Pharmaceutical Sciences, Northeastern University, Boston, Mass (T.L., V.T.).
Muneeb AhmedFrom the Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, 1 Deaconess Rd, WCC 308-B, Boston, MA 02215 (G.K., S.N.G., M.A.); Division of Image-guided Therapy and Interventional Oncology, Department of Radiology (S.N.G.), and Goldyne Savad Institute of Gene Therapy (S.G., E.G.), Hadassah Hebrew University Hospital, Jerusalem, Israel; and Department of Pharmaceutical Sciences, Northeastern University, Boston, Mass (T.L., V.T.).
Beth Israel Deaconess Medical Center · USNortheastern University · US

Funding

Physico-Chemical Nanocharacterization CoreU54CA151881 · NCI · NORTHEASTERN UNIVERSITY · PI AMIJI, MANSOOR M. · 2010 to 2014
$12.4M
Modulating systemic pro-oncogenic effects of focal image-guided tumor ablationR01CA197081 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI AHMED, MUNEEB · 2016 to 2020
$2.4M
NCI NIH HHS R01 CA197081NCI NIH HHS U54 CA151881
6 · The paper itself

Abstract

Purpose To (a) identify key expressed genes in the periablational rim after radiofrequency ablation (RFA) and their role in driving the stimulation of distant tumor growth and (b) use adjuvant drug therapies to block key identified mediator(s) to suppress off-target tumorigenic effects of hepatic RFA. Materials and Methods This institutional animal care and use committee-approved study was performed in C57BL6 mice (n = 20) and F344 rats (n = 124). First, gene expression analysis was performed in mice after hepatic RFA or sham procedure; mice were sacrificed 24 hours to 7 days after treatment. Data were analyzed for differentially expressed genes (greater than twofold change) and their functional annotations. Next, animals were allocated to hepatic RFA or sham treatment with or without STAT3 (signal transducer and activator of transcription 3) inhibitor S3I-201 for periablational phosphorylated STAT3 immunohistochemistry analysis at 24 hours. Finally, animals with subcutaneous R3230 adenocarcinoma tumors were allocated to RFA or sham treatment with or without a STAT3 inhibitor (S3I-201 or micellar curcumin, eight arms). Outcomes included distant tumor growth, proliferation (Ki-67 percentage), and microvascular density. Results At 24 hours, 217 genes had altered expression (107 upregulated and 110 downregulated), decreasing to 55 genes (27 upregulated and 28 downregulated) and 18 genes (four upregulated, 14 downregulated) at 72 hours and 7 days, respectively. At 24 hours, STAT3 occurred in four of seven activated pathways associated with pro-oncogenic genes at network analysis. Immunohistochemistry analysis confirmed elevated periablational phosphorylated STAT3 24 hours after RFA, which was suppressed with S3I-201 (percentage of positive cells per field: 31.7% ± 3.4 vs 3.8% ± 1.7; P < .001). Combined RFA plus S3I-201 reduced systemic distant tumor growth at 7 days (end diameter: 11.8 mm ± 0.5 with RFA plus S3I-201, 19.8 mm ± 0.7 with RFA alone, and 15 mm ± 0.7 with sham procedure; P < .001). STAT3 inhibition with micellar curcumin also suppressed postablation stimulation of distant tumor growth, proliferation, and microvascular density (P < .01). Conclusion Gene expression analysis identified multiple pathways upregulated in the periablational rim after hepatic RFA, of which STAT3 was active in four of seven. Postablation STAT3 activation is linked to increased distant tumor stimulation and can be suppressed with adjuvant STAT3 inhibitors.

Indexed as

Catheter AblationAdenocarcinomaAminosalicylic AcidsAnimalsBenzenesulfonatesCarcinogenesisCell Transformation, NeoplasticChemotherapy, AdjuvantDisease Models, AnimalDown-RegulationFemaleGene ExpressionLiver Neoplasms, ExperimentalMammary Neoplasms, ExperimentalMice, Inbred C57BLMicrovesselsAminosalicylic AcidsBenzenesulfonatesNSC 74859Oncogene ProteinsSTAT3 Transcription Factor

Identifiers

PMID28880787
PMCPMC5790305
OpenAlexW2752426529

What OpenQuestion holds

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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.