Evidence map›Paper›PMID 30563080›Full record

ArticleCancers2018

Obatoclax and Paclitaxel Synergistically Induce Apoptosis and Overcome Paclitaxel Resistance in Urothelial Cancer Cells.

Rocío Jiménez-Guerrero, Jessica Gasca, M Luz Flores, Begoña Pérez-Valderrama, Cristina Tejera-Parrado, Rafael Medina, María Tortolero, Francisco Romero, Miguel A Japón, Carmen Sáez

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing 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

17 citing papers in PubMed, 33 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. BH3-mimetics: recent developments in cancer therapy.Journal of experimental & clinical cancer research : CR · 2021
    Review
  8. Contrast effects of autophagy in the treatment of bladder cancer.Experimental biology and medicine (Maywood, N.J.) · 2021
    Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Review
  15. Next-generation paclitaxel-nanoparticle formulation for pancreatic cancer treatment.Nanomedicine : nanotechnology, biology, and medicine · 2019
    Article
  16. Article
  17. Article
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

10 authors at 3 institutions in 1 country.

Rocío Jiménez-GuerreroInstituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Seville, Spain. rjimenez-ibis@us.es.
Jessica GascaInstituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Seville, Spain. jgasca-ibis@us.es.
M Luz FloresInstituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Seville, Spain. mflores-ibis@us.es.ORCID 0000-0003-2674-7164
Begoña Pérez-ValderramaDepartment of Oncology, Hospital Universitario Virgen del Rocío, 41013 Seville, Spain. bperezv@gmail.com.
Cristina Tejera-ParradoInstituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Seville, Spain. ctejera-ibis@us.es.
Rafael MedinaDepartment of Urology, Hospital Universitario Virgen del Rocío, 41013 Seville, Spain. rantonio.medina.sspa@juntadeandalucia.es.ORCID 0000-0002-4514-4329
María TortoleroDepartment of Microbiology, Faculty of Biology, Universidad de Sevilla, 41012 Seville, Spain. torto@us.es.
Francisco RomeroDepartment of Microbiology, Faculty of Biology, Universidad de Sevilla, 41012 Seville, Spain. frport@us.es.
Miguel A JapónInstituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Seville, Spain. mjapon@cica.es.
Carmen SáezInstituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Seville, Spain. csaez1@us.es.ORCID 0000-0002-8600-0508
Instituto de Biomedicina de Sevilla · ESHospital Universitario Virgen del Rocío · ESUniversidad de Sevilla · ES

Funding

Consejería de Educación, Ciencia y Empresa, Junta de Andalucía P10-CTS-6243Instituto de Salud Carlos III FIS PI13/02282Instituto de Salud Carlos III PI17/1240Ministerio de Economía y Competitividad SAF2014-53799-C2-1/2-RMinisterio de Economía y Competitividad SAF2017-87358-C2-1/2-R
6 · The paper itself

Abstract

Paclitaxel is a treatment option for advanced or metastatic bladder cancer after the failure of first-line cisplatin and gemcitabine, although resistance limits its clinical benefits. Mcl-1 is an anti-apoptotic protein that promotes resistance to paclitaxel in different tumors. Obatoclax, a BH3 mimetic of the Bcl-2 family of proteins, antagonizes Mcl-1 and hence may reverse paclitaxel resistance in Mcl-1-overexpressing tumors. In this study, paclitaxel-sensitive 5637 and -resistant HT1197 bladder cancer cells were treated with paclitaxel, obatoclax, or combinations of both. Apoptosis, cell cycle, and autophagy were measured by Western blot, flow cytometry, and fluorescence microscopy. Moreover, Mcl-1 expression was analyzed by immunohistochemistry in bladder carcinoma tissues. Our results confirmed that paclitaxel alone induced Mcl-1 downregulation and apoptosis in 5637, but not in HT1197 cells; however, combinations of obatoclax and paclitaxel sensitized HT1197 cells to the treatment. In obatoclax-treated 5637 and obatoclax + paclitaxel-treated HT1197 cells, the blockade of the autophagic flux correlated with apoptosis and was associated with caspase-dependent cleavage of beclin-1. Obatoclax alone delayed the cell cycle in 5637, but not in HT1197 cells, whereas combinations of both retarded the cell cycle and reduced mitotic slippage. In conclusion, obatoclax sensitizes HT1197 cells to paclitaxel-induced apoptosis through the blockade of the autophagic flux and effects on the cell cycle. Furthermore, Mcl-1 is overexpressed in many invasive bladder carcinomas, and it is related to tumor progression, so Mcl-1 expression may be of predictive value in bladder cancer.

Indexed as

apoptosisautophagybladder cancerobatoclaxpaclitaxel

Identifiers

PMID30563080
PMCPMC6316685
OpenAlexW2902377934

What OpenQuestion holds

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LicenceCC BY
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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.