ArticleJournal of oncology2013
Mammalian target of rapamycin inhibitors induce tumor cell apoptosis in vivo primarily by inhibiting VEGF expression and angiogenesis.
Article in Journal of oncology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Can Targeting Hypoxia-Mediated Acidification of the Bone Marrow Microenvironment Kill Myeloma Tumor Cells?Frontiers in oncology · 2021Pooled it
- Acidification of intracellular pH in MM tumor cells overcomes resistance to hypoxia-mediated apoptosisFrontiers in oncology · 2023Article
- Recent advances of nanotechnology-based tumor vessel-targeting strategies.Journal of nanobiotechnology · 2021Review
- Phase 1 trial of vorolanib (CM082) in combination with everolimus in patients with advanced clear-cell renal cell carcinoma.EBioMedicine · 2020Article
- Multimodal Bioluminescent and Positronic-emission Tomography/Computational Tomography Imaging of Multiple Myeloma Bone Marrow Xenografts in NOG Mice.Journal of visualized experiments : JoVE · 2019Article
- Synchronous inhibition of mTOR and VEGF/NRP1 axis impedes tumor growth and metastasis in renal cancer.NPJ precision oncology · 2019Article
- Article
- [Effects of hypoxia-inducible factor 1α on hypoxic tolerance of human amniotic mesenchymal stem cells].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2018Article
- Portal branch ligation does not counteract the inhibiting effect of temsirolimus on extrahepatic colorectal metastatic growth.Clinical & experimental metastasis · 2017Article
- The hypoxia signalling pathway in haematological malignancies.Oncotarget · 2017Review
- Article
- A DNA-binding Molecule Targeting the Adaptive Hypoxic Response in Multiple Myeloma Has Potent Antitumor Activity.Molecular cancer research : MCR · 2016Article
- Improvement of tuberous sclerosis complex (TSC) skin tumors during long-term treatment with oral sirolimus.Journal of the American Academy of Dermatology · 2015Article
- Tumour growth of colorectal rat liver metastases is inhibited by hepatic arterial infusion of the mTOR-inhibitor temsirolimus after portal branch ligation.Clinical & experimental metastasis · 2015Article
- Efficacy and safety of a mammalian target of rapamycin inhibitor in pediatric patients with tuberous sclerosis complex: A systematic review and meta-analysis.Experimental and therapeutic medicine · 2015Article
- Fisetin targets phosphatidylinositol-3-kinase and induces apoptosis of human B lymphoma Raji cells.Toxicology reports · 2015Article
- Article
- Anti-Angiogenic Drugs: Involvement in Cutaneous Side Effects and Wound-Healing Complication.Advances in wound care · 2014Review
- Phospho-mTOR in non-tumour and tumour bladder urothelium: Pattern of expression and impact on urothelial bladder cancer patients.Oncology letters · 2014Article
- mTOR pathway in colorectal cancer: an update.Oncotarget · 2014Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
We found that rapalog mTOR inhibitors induce G1 arrest in the PTEN-null HS Sultan B-cell lymphoma line in vitro, but that administration of rapalogs in a HS Sultan xenograft model resulted in significant apoptosis, and that this correlated with induction of hypoxia and inhibition of neoangiogenesis and VEGF expression. Mechanistically, rapalogs prevent cap-dependent translation, but studies have shown that cap-independent, internal ribosome entry site (IRES)-mediated translation of genes, such as c-myc and cyclin D, can provide a fail-safe mechanism that regulates tumor survival. Therefore, we tested if IRES-dependent expression of VEGF could likewise regulate sensitivity of tumor cells in vivo. To achieve this, we developed isogenic HS Sultan cell lines that ectopically express the VEGF ORF fused to the p27 IRES, an IRES sequence that is insensitive to AKT-mediated inhibition of IRES activity and effective in PTEN-null tumors. Mice challenged with p27-VEGF transfected tumor cells were more resistant to the antiangiogenic and apoptotic effects of the rapalog, temsirolimus, and active site mTOR inhibitor, pp242. Our results confirm the critical role of VEGF expression in tumors during treatment with mTOR inhibitors and underscore the importance of IRES activity as a resistance mechanism to such targeted therapy.
Identifiers
What OpenQuestion holds
Registered trials
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.