ArticleProceedings of the National Academy of Sciences of the United States of America2003
Antisense therapy targeting MDM2 oncogene in prostate cancer: Effects on proliferation, apoptosis, multiple gene expression, and chemotherapy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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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.
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.
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Who cites it
84 citing papers in PubMed, 193 citations in OpenAlex.
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- METTL3-mediated mCellular & molecular biology letters · 2024Article
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- Stem Cells as Target for Prostate cancer Therapy: Opportunities and Challenges.Stem cell reviews and reports · 2022Review
- Potential roles of PIWI-interacting RNAs in lung cancer.Frontiers in oncology · 2022Review
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- PARP and CDK4/6 Inhibitor Combination Therapy Induces Apoptosis and Suppresses Neuroendocrine Differentiation in Prostate Cancer.Molecular cancer therapeutics · 2021Article
- Anti-malarial drug: the emerging role of artemisinin and its derivatives in liver disease treatment.Chinese medicine · 2021Review
- VEGF-A/VEGF-B/VEGF-C expressions in non-hereditary, non-metastatic phaeochromocytoma.Histology and histopathology · 2021Article
- Targeting the p53-MDM2 pathway for neuroblastoma therapy: Rays of hope.Cancer letters · 2021Review
- TRIM31 enhances chemoresistance in glioblastoma through activation of the PI3K/Akt signaling pathway.Experimental and therapeutic medicine · 2020Article
- Urolithin A induces prostate cancer cell death in p53-dependent and in p53-independent manner.European journal of nutrition · 2020Article
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- Biochemical and molecular aspects of 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis: a review.Toxicology research · 2020Review
- A novel inhibitor of MDM2 oncogene blocks metastasis of hepatocellular carcinoma and overcomes chemoresistance.Genes & diseases · 2019Article
- Polydatin Encapsulated Poly [Lactic-co-glycolic acid] Nanoformulation Counteract the 7,12-Dimethylbenz[a] Anthracene Mediated Experimental Carcinogenesis through the Inhibition of Cell Proliferation.Antioxidants (Basel, Switzerland) · 2019Article
- MEG3: an Oncogenic Long Non-coding RNA in Different Cancers.Pathology oncology research : POR · 2019Review
- Epigenetic roles of PIWI proteins and piRNAs in lung cancer.Cell & bioscience · 2019Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
This study was undertaken to investigate the role of mouse double minute 2 (MDM2) oncogene in prostate cancer growth and the potential of MDM2 as a target for prostate cancer therapy. An antisense anti-human-MDM2 mixed-backbone oligonucleotide was tested in human prostate cancer models with various p53 statuses, LNCaP (p53wt/wt), DU145 (p53mt/mt), and PC3 (p53null). In a dose- and time-dependent manner, it specifically inhibited MDM2 expression and modified expression of several genes, at both mRNA and protein levels. In LNCaP cells, p53, p21, Bax, and hypophosphorylated retinoblastoma tumor suppressor protein (pRb) levels increased, whereas Bcl2, pRb protein, and E2F transcription factor 1 (E2F1) levels decreased. In DU145 cells, p21 levels were elevated and E2F1 levels decreased, although mutant p53, Rb, and Bax levels remained unchanged. In PC3 cells, MDM2 inhibition resulted in elevated p21, Bax, and pRb levels and decreased ppRb and E2F1 levels. In all three cell lines, MDM2 inhibition reduced cell proliferation, induced apoptosis, and potentiated the effects of the chemotherapeutic agents 10-hydroxycamptothecin and paclitaxel. The anti-MDM2 oligonucleotide showed antitumor activity and increased therapeutic effectiveness of paclitaxel in both LNCaP and PC3 xenografts, causing changes in gene expression similar to those seen in vitro. In summary, this study demonstrates that MDM2 has a role in prostate cancer growth via p53-dependent and p53-independent mechanisms and that multiple genes are involved in the process. MDM2 inhibitors such as second-generation antisense oligonucleotides have a broad spectrum of antitumor activities in human cancers regardless of p53 status, providing novel approaches to therapy of human prostate cancer.
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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.