Evidence map›Paper›PMID 35247260›Full record

ArticleThe Journal of clinical endocrinology and metabolism2022

The p300 Inhibitor A-485 Exerts Antitumor Activity in Growth Hormone Pituitary Adenoma.

Chenxing Ji, Wen Xu, Hong Ding, Zhengyuan Chen, Chengzhang Shi, Jie Han, Liang Yu, Nidan Qiao, Yichao Zhang, Xiaoyun Cao and 8 more

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

Article in The Journal of clinical endocrinology and metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
4.0field-weighted citation impact, top 5% 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

23 citing papers in PubMed, 30 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

18 authors at 4 institutions in 1 country.

Chenxing JiDepartment of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, National Center for Neurological Disorders, Shanghai, China.ORCID 0000-0003-1226-5658
Wen XuHospital & Institute of Obstetrics and Gynecology, Fudan University, Shanghai, China.
Hong DingDepartment of Medicinal Chemistry, China Pharmaceutical University, Nanjing, China.
Zhengyuan ChenDepartment of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, National Center for Neurological Disorders, Shanghai, China.
Chengzhang ShiDepartment of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, National Center for Neurological Disorders, Shanghai, China.
Jie HanDrug Discovery and Design Center, CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Liang YuDrug Discovery and Design Center, CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Nidan QiaoDepartment of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, National Center for Neurological Disorders, Shanghai, China.
Yichao ZhangDepartment of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, National Center for Neurological Disorders, Shanghai, China.
Xiaoyun CaoDepartment of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, National Center for Neurological Disorders, Shanghai, China.
Xiang ZhouDepartment of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, National Center for Neurological Disorders, Shanghai, China.
Haixia ChengDepartment of Pathology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Huijin FengDepartment of Medicinal Chemistry, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Cheng LuoDrug Discovery and Design Center, CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Zhiyu LiDepartment of Medicinal Chemistry, China Pharmaceutical University, Nanjing, China.ORCID 0000-0001-6492-9511
Bing ZhouDepartment of Medicinal Chemistry, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.ORCID 0000-0003-1813-8035
Zhao YeDepartment of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, National Center for Neurological Disorders, Shanghai, China.ORCID 0000-0001-9401-3993
Yao ZhaoDepartment of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, National Center for Neurological Disorders, Shanghai, China.
Fudan University · CNChinese Academy of Sciences · CNChina Pharmaceutical University · CNObstetrics and Gynecology Hospital of Fudan University · CN

Funding

Ministry of Science and Technology of the People's Republic of ChinaNational High Technology Research and Development Program of China 2014AA020611National Key Research and Development Program of China 2017YFB0202600National Natural Science Foundation of China 81802496National Science Fund for Distinguished Young Scholars 81725011Strategic Priority Research Program of the Chinese Academy of Sciences XDA12020368
6 · The paper itself

Abstract

contextGrowth hormone pituitary adenoma (GHPA), a major subtype of pituitary adenoma (PA), can lead to progressive somatic disfigurement, multiple complications, and even increased mortality. The efficacy of current treatments is limited; thus, a novel pharmacological treatment is urgently needed. As a histone acetyltransferase (HAT) coactivator, p300 can regulate the transcription of several genes that are crucial for PA tumorigenesis and progression. However, the role of p300 and its catalytic inhibitor in GHPA is still unclear.

objectiveWe aimed to identify the expression of p300 in GHPA and in normal pituitary glands.

methodsThe expression of p300 was detected in GHPA and normal pituitary tissues. Genetic knockdown was performed by siRNA. The efficacy of the p300 inhibitor A-485 in the cell cycle, proliferation, apoptosis, and hormone secretion was investigated by flow cytometry, ELISAs, Western blotting, and qRT-PCR. RNA sequencing, bioinformatic analysis, and subsequent validation experiments were performed to reveal the potential biological mechanism of A-485.

resultsHigh expression of p300 was found in GHPA tissues compared with normal pituitary tissues. Knockdown of p300 inhibited cell proliferation and clone formation. Treatment with A-485 suppressed cell growth and inhibited the secretion of GH in vitro and in vivo. Further mechanistic studies showed that A-485 could downregulate the expression or activity of several oncogenes, such as genes in the Pttg1, c-Myc, cAMP and PI3K/AKT/mTOR signaling pathways, which are crucial for PA tumorigenesis and progression.

conclusionOur findings demonstrate that inhibition of HAT p300 by its selective inhibitor A-485 is a promising therapy for GHPA.

Indexed as

AdenomaGrowth Hormone-Secreting Pituitary AdenomaHuman Growth HormonePituitary NeoplasmsCarcinogenesisCell Line, TumorCell ProliferationGrowth HormoneHumansPhosphatidylinositol 3-KinasesGrowth HormoneHuman Growth HormonePhosphatidylinositol 3-KinasesA-485growth hormone pituitary adenomap300

Identifiers

PMID35247260
PMCPMC9113810
OpenAlexW4220787893

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.