ArticleCancer research2008
Overexpression of vascular endothelial growth factor and the development of post-transplantation cancer.
Article in Cancer research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- De novo colorectal cancer after kidney transplantation: a systematic review and meta-analysis.British journal of cancer · 2025Pooled it
- Growth Factor Signaling in Solid Organ Transplantation: A Conceptual Framework for Chronic Remodeling and Survival.International journal of molecular sciences · 2026Review
- Analyzing research trends in the relationship between immunosuppressants and cancer following organ transplantation: a bibliometric study from 2001 to 2023.Discover oncology · 2025Article
- Risk ofJournal of gastrointestinal oncology · 2024Article
- Achieving tolerance modifies cancer susceptibility profiles in liver transplant recipients.Cancer medicine · 2023Article
- Cardiovascular toxicity of tyrosine kinase inhibitors during cancer treatment: Potential involvement of TRPM7.Frontiers in cardiovascular medicine · 2023Review
- Manipulating adrenergic stress receptor signalling to enhance immunosuppression and prolong survival of vascularized composite tissue transplants.Clinical and translational medicine · 2022Article
- Calcineurin inactivation inhibits pyruvate dehydrogenase complex activity and induces the Warburg effect.Oncogene · 2021Article
- Managing immunosuppressive therapy in potentially cured post-kidney transplant cancer (excluding non-melanoma skin cancer): an overview of the available evidence and guidance for shared decision-making.Transplant international : official journal of the European Society for Organ Transplantation · 2021Review
- De Novo Cancer Incidence after Kidney Transplantation in South Korea from 2002 to 2017.Journal of clinical medicine · 2021Article
- Regression of Lung Squamous Cell Carcinoma after the Withdrawal of Cyclosporin A Combined with Pirfenidone Treatment in a Patient with Idiopathic Pulmonary Fibrosis.Internal medicine (Tokyo, Japan) · 2021Article
- Vasculogenesis from Human Dental Pulp Stem Cells Grown in Matrigel with Fully Defined Serum-Free Culture Media.Biomedicines · 2020Article
- Survival after a cancer diagnosis among solid organ transplant recipients in the United States.Cancer · 2019Article
- Signaling Molecules in Posttransplantation Cancer.Clinics in laboratory medicine · 2019Review
- Clostridium difficile toxins induce VEGF-A and vascular permeability to promote disease pathogenesis.Nature microbiology · 2019Article
- Risk of lip cancer after solid organ transplantation in the United States.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2019Article
- Cancer in kidney transplant recipients.Nature reviews. Nephrology · 2018Review
- Investigating Effect of Rapamycin and Metformin on Angiogenesis in Hepatocellular Carcinoma Cell Line.Advanced pharmaceutical bulletin · 2018Article
- Macropinocytosis of Bevacizumab by Glioblastoma Cells in the Perivascular Niche Affects their Survival.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Cancer in Solid Organ Transplant Recipients: There Is Still Much to Learn and Do.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2017Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
Cancer is an increasing and major problem after solid organ transplantation. In part, the increased cancer risk is associated with the use of immunosuppressive agents, especially calcineurin inhibitors. We propose that the effect of calcineurin inhibitors on the expression of vascular endothelial growth factor (VEGF) leads to an angiogenic milieu that favors tumor growth. Here, we used 786-0 human renal cancer cells to investigate the effect of cyclosporine (CsA) on VEGF expression. Using a full-length VEGF promoter-luciferase construct, we found that CsA markedly induced VEGF transcriptional activation through the protein kinase C (PKC) signaling pathway, specifically involving PKC zeta and PKC delta isoforms. Moreover, CsA promoted the association of PKC zeta and PKC delta with the transcription factor Sp1 as observed by immunoprecipitation assays. Using promoter deletion constructs, we found that CsA-mediated VEGF transcription was primarily Sp1 dependent. Furthermore, CsA-induced and PKC-Sp1-mediated VEGF transcriptional activation was partially inhibited by von Hippel-Lindau protein. CsA also promoted the progression of human renal tumors in vivo, wherein VEGF is overexpressed. Finally, to evaluate the in vivo significance of CsA-induced VEGF overexpression in terms of post-transplantation tumor development, we injected CT26 murine carcinoma cells (known to form angiogenic tumors) into mice with fully MHC mismatched cardiac transplants. We observed that therapeutic doses of CsA increased tumor size and VEGF mRNA expression and also enhanced tumor angiogenesis. However, coadministration of a blocking anti-VEGF antibody inhibited this CsA-mediated tumor growth. Collectively, these findings define PKC-mediated VEGF transcriptional activation as a key component in the progression of CsA-induced post-transplantation cancer.
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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.