Evidence map›Paper›PMID 31863126›Full record

ArticleCancer chemotherapy and pharmacology2020

The antimetastatic activity of orlistat is accompanied by an antitumoral immune response in mouse melanoma.

Luciana Y de Almeida, Flávia S Mariano, Débora C Bastos, Karen A Cavassani, Janna Raphelson, Vânia S Mariano, Michelle Agostini, Fernanda S Moreira, Ricardo D Coletta, Renata O Mattos-Graner and 1 more

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Article in Cancer chemotherapy and pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.8field-weighted citation impact, top 32% 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

12 citing papers in PubMed, 18 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

11 authors at 4 institutions in 2 countries.

Luciana Y de Almeida *Department of Oral Diagnosis, School of Dentistry of Piracicaba, State University of Campinas (UNICAMP), Piracicaba, São Paulo, Brazil. Av. Limeira 901, CP 52, Areão, Piracicaba, SP, 13414-903, Brazil.
Flávia S Mariano *Department of Oral Diagnosis, School of Dentistry of Piracicaba, State University of Campinas (UNICAMP), Piracicaba, São Paulo, Brazil. Av. Limeira 901, CP 52, Areão, Piracicaba, SP, 13414-903, Brazil.
Débora C BastosDepartment of Oral Diagnosis, School of Dentistry of Piracicaba, State University of Campinas (UNICAMP), Piracicaba, São Paulo, Brazil. Av. Limeira 901, CP 52, Areão, Piracicaba, SP, 13414-903, Brazil.
Karen A CavassaniUrologic Oncology Program/Uro-Oncology Research Laboratories, Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, 90048, USA.
Janna RaphelsonUrologic Oncology Program/Uro-Oncology Research Laboratories, Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, 90048, USA.
Vânia S MarianoDepartment of Basic and Applied Immunology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
Michelle AgostiniDepartment of Oral Diagnosis and Pathology, School of Dentistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Fernanda S MoreiraDepartment of Oral Diagnosis, School of Dentistry of Piracicaba, State University of Campinas (UNICAMP), Piracicaba, São Paulo, Brazil. Av. Limeira 901, CP 52, Areão, Piracicaba, SP, 13414-903, Brazil.
Ricardo D ColettaDepartment of Oral Diagnosis, School of Dentistry of Piracicaba, State University of Campinas (UNICAMP), Piracicaba, São Paulo, Brazil. Av. Limeira 901, CP 52, Areão, Piracicaba, SP, 13414-903, Brazil.
Renata O Mattos-GranerDepartment of Oral Diagnosis, School of Dentistry of Piracicaba, State University of Campinas (UNICAMP), Piracicaba, São Paulo, Brazil. Av. Limeira 901, CP 52, Areão, Piracicaba, SP, 13414-903, Brazil.
Edgard GranerDepartment of Oral Diagnosis, School of Dentistry of Piracicaba, State University of Campinas (UNICAMP), Piracicaba, São Paulo, Brazil. Av. Limeira 901, CP 52, Areão, Piracicaba, SP, 13414-903, Brazil. graner@unicamp.br.
Universidade Estadual de Campinas (UNICAMP) · BRCedars-Sinai Medical Center · USUniversidade de São Paulo · BRUniversidade Federal do Rio de Janeiro · BR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeFatty acid synthase (FASN), the multifunctional enzyme responsible for endogenous fatty acid synthesis, is highly expressed and associated with poor prognosis in several human cancers, including melanoma. Our group has previously shown that pharmacological inhibition of FASN with orlistat decreases proliferation, promotes apoptosis, and reduces the metastatic spread of B16-F10 cells in experimental models of melanoma. While most of the orlistat antitumor properties seem to be closely related to direct effects on malignant cells, its impact on the host immune system is still unknown.

methodsThe effects of orlistat on the phenotype and activation status of infiltrating leukocytes in primary tumors and metastatic lymph nodes were assessed using a model of spontaneous melanoma metastasis (B16-F10 cells/C57BL/6 mice). Cells from the primary tumors and lymph nodes were mechanically dissociated and immune cells phenotyped by flow cytometry. The expression of IL-12p35, IL-12p40, and inducible nitric oxide synthase (iNOS) was analyzed by qRT-PCR and production of nitrite (NO

resultsOrlistat-treated mice exhibited a 25% reduction in the number of mediastinal lymph node metastases (mean 3.96 ± 0.78, 95% CI 3.63-4.28) compared to the controls (mean 5.7 ± 1.72; 95% CI 5.01-6.43). The drug elicited an antitumor immune response against experimental melanomas by increasing maturation of intratumoral dendritic cells (DC), stimulating the expression of cytotoxicity markers in CD8 T lymphocytes and natural killer (NK) cells, as well as reducing regulatory T cells (Tregs). Moreover, the orlistat-treatment increased serum levels of nitric oxide (NO) concentrations.

conclusionTaken together, these findings suggest that orlistat supports an antitumor response against experimental melanomas by increasing CD80/CD81-positive and IL-12-positive DC populations, granzyme b/NKG2D-positive NK populations, and perforin/granzyme b-positive CD8 T lymphocytes as well as reducing Tregs counts within experimental melanomas.

Indexed as

AnimalsAntineoplastic AgentsApoptosisCD8-Positive T-LymphocytesCell Line, TumorCell ProliferationDendritic CellsFatty Acid SynthasesKiller Cells, NaturalLymphatic MetastasisMaleMelanoma, ExperimentalMiceMice, Inbred C57BLNitric OxideOrlistatAntineoplastic AgentsFatty Acid SynthasesNitric OxideOrlistatExperimental melanomaFatty acid synthaseImmune responseMetastasisOrlistat

Identifiers

PMID31863126
OpenAlexW2995804660

What OpenQuestion holds

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Registered trials

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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.