Evidence map›Paper›PMID 23995783›Full record

ArticleOncogene2014

Macrophages mediate gemcitabine resistance of pancreatic adenocarcinoma by upregulating cytidine deaminase.

N Weizman, Y Krelin, A Shabtay-Orbach, M Amit, Y Binenbaum, R J Wong, Z Gil

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 166 papers.

0numbers the graph read from it
0cells of the map it votes in
166citing papers in PubMed
7.2field-weighted citation impact, top 2% 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

166 citing papers in PubMed, 276 citations in OpenAlex.

  1. Article
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  5. Immune cell metabolism in cancer drug resistance: Advances in target discovery and clinical translation.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2025
    Article
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  10. A glycogen derived from sea urchin-Frontiers in pharmacology · 2025
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106 more citing papers are in PubMed but not listed here.

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

7 authors at 3 institutions in 2 countries.

N WeizmanThe Laboratory for Applied Cancer Research, Department of Otolaryngology Head and Neck Surgery, Rambam Medical Center, Haifa, Israel.
Y KrelinThe Laboratory for Applied Cancer Research, Department of Otolaryngology Head and Neck Surgery, Rambam Medical Center, Haifa, Israel.
A Shabtay-OrbachThe Laboratory for Applied Cancer Research, Department of Otolaryngology Head and Neck Surgery, Rambam Medical Center, Haifa, Israel.
M Amit1] The Laboratory for Applied Cancer Research, Department of Otolaryngology Head and Neck Surgery, Rambam Medical Center, Haifa, Israel [2] Department of Otolaryngology Head and Neck Surgery, Rambam Medical Center, The Technion Israel Institute of Technology, Haifa, Israel.
Y BinenbaumThe Laboratory for Applied Cancer Research, Department of Otolaryngology Head and Neck Surgery, Rambam Medical Center, Haifa, Israel.
R J WongDepartment of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Z Gil1] The Laboratory for Applied Cancer Research, Department of Otolaryngology Head and Neck Surgery, Rambam Medical Center, Haifa, Israel [2] Department of Otolaryngology Head and Neck Surgery, Rambam Medical Center, The Technion Israel Institute of Technology, Haifa, Israel.
Rambam Health Care Campus · ILMemorial Sloan Kettering Cancer Center · USTechnion – Israel Institute of Technology · IL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Resistance to pharmacologic agents used in chemotherapy is common in most human carcinomas, including pancreatic ductal adenocarcinoma (PDA), which is resistant to almost all drugs, including gemcitabine, a nucleoside analog used as a first-line treatment. Poor survival rates of PDA patients have, therefore, not changed much over 4 decades. Recent data indicated that tumor-associated macrophages (TAMs), which are abundant in the microenvironment of several tumors, including PDA, secrete pro-tumorigenic factors that contribute to cancer progression and dissemination. In this study, we show for the first time that TAMs can also induce chemoresistance of PDA by reducing gemcitabine-induced apoptosis. Macrophages co-cultured with cancer cells or TAM-conditioned medium significantly reduced apoptosis and activation of the caspase-3 pathway during gemcitabine treatment. In vivo PDA models of mice, which have reduced macrophage recruitment and activation, demonstrated improved response to gemcitabine compared with controls. Similarly, inhibition of monocytes/macrophages trafficking by a CSF1-receptor antagonist GW2580 augmented the effect of gemcitabine in a transgenic mouse PDA model that was resistant to gemcitabine alone. Analysis of multiple proteins involved in gemcitabine delivery and metabolism revealed that TAMs induced upregulation of cytidine deaminase (CDA), the enzyme that metabolizes the drug following its transport into the cell. Decreasing CDA expression by PDA cells blocked the protective effect of TAMs against gemcitabine. These results provide the first evidence of a paracrine effect of TAMs, which mediates acquired resistance of cancer cells to chemotherapy. Modulation of macrophage trafficking or inhibition of CDA may offer a new strategy for augmenting the response of PDA to chemotherapy.

Indexed as

Drug Resistance, NeoplasmAdenocarcinomaAnimalsAntimetabolites, AntineoplasticCell Line, TumorCytidine DeaminaseDeoxycytidineDisease Models, AnimalDose-Response Relationship, DrugFemaleGemcitabineHumansMacrophagesMiceMice, KnockoutPancreatic NeoplasmsAntimetabolites, AntineoplasticCytidine DeaminaseDeoxycytidineGemcitabineReceptors, Granulocyte-Macrophage Colony-Stimulating Factor

Identifiers

PMID23995783
OpenAlexW2032131517

What OpenQuestion holds

Textmetadata
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.