Evidence map›Paper›PMID 25477070›Full record

ArticleJournal of hematology & oncology2014

c-FLIP is involved in tumor progression of peripheral T-cell lymphoma and targeted by histone deacetylase inhibitors.

Zhong Zheng, Shu Cheng, Wen Wu, Li Wang, Yan Zhao, Yang Shen, Anne Janin, Wei-Li Zhao

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

Article in Journal of hematology & oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing 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

20 citing papers in PubMed, 31 citations in OpenAlex.

  1. Review
  2. Article
  3. Valproic Acid Inhibits Peripheral T Cell Lymphoma Cells Behaviors via Restraining PI3K/AKT Pathway.Evidence-based complementary and alternative medicine : eCAM · 2022
    Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Immunohistopathological Study of c-FLIP Protein in Mycosis FungoidesAsian Pacific journal of cancer prevention : APJCP · 2017
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Belinostat for Relapsed or Refractory Peripheral T-Cell Lymphoma.Journal of the advanced practitioner in oncology · 2016
    Review
  17. Article
  18. Conferone, a coumarin fromInternational journal of immunopathology and pharmacology
    Article
  19. Review
  20. 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

8 authors at 2 institutions in 1 country.

Zhong ZhengState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Er Road, Shanghai, 200025, China. zheng_zhong89@163.com.
Shu ChengState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Er Road, Shanghai, 200025, China. orenge@medmail.com.cn.
Wen WuState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Er Road, Shanghai, 200025, China. wuwen@medmail.com.cn.
Li WangState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Er Road, Shanghai, 200025, China. wl_wangdong@126.com.
Yan ZhaoState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Er Road, Shanghai, 200025, China. joyce19890611@163.com.
Yang ShenState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Er Road, Shanghai, 200025, China. shen_yang@126.com.
Anne JaninPôle de Recherches Sino-Français en Science du Vivant et Génomique, Laboratory of Molecular Pathology, Shanghai, China. anne_janin@yahoo.com.
Wei-Li ZhaoState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Er Road, Shanghai, 200025, China. zhao.weili@yahoo.com.
Shanghai Institute of Hematology · CNShanghai Jiao Tong University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPeripheral T-cell lymphomas (PTCLs) are often aggressive tumors and resistant to conventional chemotherapy. Dysregulation of extrinsic apoptosis plays an important role on tumor cell sensitivity to chemotherapeutic agents. Cellular FLICE inhibitory protein (c-FLIP) is a key regulator of extrinsic apoptotic pathway.

methodsc-FLIP expression was assessed by real-time PCR and compared according to clinical parameters in patients with PTCLs. The relation of c-FLIP to tumor cell apoptosis mediated by histone deacetylases inhibitors (HDACIs) and the possible mechanism were examined in T-lymphoma cell lines and in a murine xenograft model.

resultsc-FLIP was overexpressed and associated with decreased tumor TRAIL/DR5 expression, elevated serum lactate dehydrogenase level and high-risk International Prognostic Index of the patients. In vitro, molecular silencing of c-FLIP by specific small-interfering RNA increased TRAIL/DR5 expression, enhanced T-lymphoma cell apoptosis and sensitized cells to chemotherapeutic agents. However, HDACIs valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA) could downregulate c-FLIP expression and triggered extrinsic apoptosis of T-lymphoma cells, through inhibiting NF-κB signaling and interrupting P50 interaction with c-FLIP promoter. As Class I HDACIs, both VPA and SAHA inhibited HDAC1, resulting in P50 inactivation and c-FLIP downregulation. In vivo, oral VPA treatment significantly retarded tumor growth and induced in situ apoptosis, consistent with inhibition of HDAC1/P50/c-FLIP axis and increase of TRAIL/DR5 expression.

conclusionsc-FLIP overexpression in PTCLs protected tumor cells from extrinsic apoptosis and contributed to tumor progression. Although linking to chemoresistance, c-FLIP indicated tumor cell sensitivity to HDACIs, providing a potential biomarker of targeting apoptosis in treating PTCLs.

Indexed as

ApoptosisCASP8 and FADD-Like Apoptosis Regulating ProteinCell Line, TumorDisease ProgressionHEK293 CellsHistone Deacetylase InhibitorsHumansJurkat CellsLymphoma, T-Cell, PeripheralMolecular Targeted TherapySignal TransductionCASP8 and FADD-Like Apoptosis Regulating ProteinHistone Deacetylase Inhibitors

Identifiers

PMID25477070
PMCPMC4261569
OpenAlexW2164103344

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.