Trial reportAngiogenesis2020
Constitutively active PIK3CA mutations are expressed by lymphatic and vascular endothelial cells in capillary lymphatic venous malformation.
Trial report in Angiogenesis, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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
34 citing papers in PubMed, 54 citations in OpenAlex.
- Bleomycin ElectroScleroTherapy (BEST): mechanistic parallels to electrochemotherapy, experimental models, and unresolved questions.Radiology and oncology · 2026Review
- Identification of pathological CD133+ endothelial cells in venous malformations.Frontiers in cardiovascular medicine · 2026Article
- Advances in genetics, signaling, and modeling of venous malformations.Frontiers in cardiovascular medicine · 2026Review
- PI3K/AKT/mTOR axis in vascular malformations: from molecular insights to targeted clinical trials.Orphanet journal of rare diseases · 2025Review
- Ultra-deep targeted next-generation sequencing with peripheral blood in patients with vascular malformations: a cohort of 40 patients.Molecular biology reports · 2025Article
- Effective Sirolimus Use in Prenatal and Postnatal Management of Symptomatic Extensive Congenital Capillary-Lymphatic-Venous Malformations (CLVMs): A Report of Two Cases.Paediatric drugs · 2025Article
- Angiopoietin-TIE2 feedforward circuit promotes PIK3CA-driven venous malformations.Nature cardiovascular research · 2025Article
- Identification of Somatic Genetic Variants in Superficial Vascular Malformations by Liquid Biopsy in a Cohort of 88 Patients from a French Hospital.Molecular diagnosis & therapy · 2025Article
- Cerebral Cavernous Malformation: From Genetics to Pharmacotherapy.Brain and behavior · 2025Review
- Targeted therapies for vascular malformations.Frontiers in medicine · 2024Review
- Three-dimensional visualization of the lymphatic, vascular and neural network in rat lung by confocal microscopy.Journal of molecular histology · 2023Article
- Targeted next-generation sequencing for detection of PIK3CA mutations in archival tissues from patients with Klippel-Trenaunay syndrome in an Asian population : List the full names and institutional addresses for all authors.Orphanet journal of rare diseases · 2023Article
- Pathological angiogenesis: mechanisms and therapeutic strategies.Angiogenesis · 2023Review
- Familial CCM Genes Might Not Be Main Drivers for Pathogenesis of Sporadic CCMs-Genetic Similarity between Cancers and Vascular Malformations.Journal of personalized medicine · 2023Review
- Review of diagnosis, differential diagnosis, and management of retroperitoneal lymphangioma.Japanese journal of radiology · 2023Review
- Microphysiological model of PIK3CA-driven vascular malformations reveals a role of dysregulated Rac1 and mTORC1/2 in lesion formation.Science advances · 2023Article
- The Genetic Architecture of Vascular Anomalies: Current Data and Future Therapeutic Perspectives Correlated with Molecular Mechanisms.International journal of molecular sciences · 2022Review
- NRASAngiogenesis · 2022Article
- How we approach the use of sirolimus and new agents: Medical therapy to treat vascular anomalies.Pediatric blood & cancer · 2022Article
- Osteopathy in Complex Lymphatic Anomalies.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Capillary lymphatic venous malformations (CLVM) are complex vascular anomalies characterized by aberrant and enlarged lymphatic and blood vessels. CLVM appear during fetal development and enlarge after birth, causing life-long complications such as coagulopathy, pulmonary embolism, chronic pain, and disfigurement. Treatment includes surgical debulking, amputation, and recurrent sclerotherapy. Somatic, mosaic mutations in the 110-kD catalytic α-subunit of phosphoinositide-3-kinase (PIK3CA) gene have been previously identified in affected tissues from CLVM patients; however, the cell population harboring the mutation is still unknown. In this study, we hypothesized that endothelial cells (EC) carry the PIK3CA mutations and play a major role in the cellular origin of CLVM. We isolated EC from the lesions of seven patients with CLVM and identified PIK3CA hotspot mutations. The CLVM EC exhibited constitutive phosphorylation of the PI3K effector AKT as well as hyperproliferation and increased resistance to cell death compared to normal EC. Inhibitors of PIK3CA (BYL719) and AKT (ARQ092) attenuated the proliferation of CLVM EC in a dose-dependent manner. A xenograft model of CLVM was developed by injecting patient-derived EC into the flanks of immunocompromised mice. CLVM EC formed lesions with enlarged lymphatic and vascular channels, recapitulating the patient histology. EC subpopulations were further obtained by both immunomagnetic separation into lymphatic EC (LEC) and vascular EC (VEC) and generation of clonal populations. By sequencing these subpopulations, we determined that both LEC and VEC from the same patient express the PIK3CA mutation, exhibit increased AKT activation and can form lymphatic or vascular lesions in mouse.
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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 Socratic graph.