ArticleDigestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver2009
Estrogens stimulate the proliferation of human cholangiocarcinoma by inducing the expression and secretion of vascular endothelial growth factor.
Article in Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled 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.
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
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Exogenous hormone use, reproductive factors and risk of intrahepatic cholangiocarcinoma among women: results from cohort studies in the Liver Cancer Pooling Project and the UK Biobank.British journal of cancer · 2020Pooled it
- Sexual dimorphism in the liver.Nature reviews. Gastroenterology & hepatology · 2026Review
- 27-Hydroxycholesterol in bile duct tissue promotes cholangiocarcinoma progression through estrogen receptor signaling.American journal of cancer research · 2026Article
- Mucinous cystic neoplasms of the pancreas demonstrateFrontiers in cell and developmental biology · 2025Article
- Interplay of Cardiometabolic Syndrome and Biliary Tract Cancer: A Comprehensive Analysis with Gender-Specific Insights.Cancers · 2024Review
- An Examination of Liver Cancer Incidence in California.Journal of registry management · 2024Article
- scAAV9-VEGF alleviates symptoms of amyotrophic lateral sclerosis (ALS) mice through regulating aromatase.Experimental brain research · 2023Article
- Article
- Pre- and Post-Sexual Maturity Liver-specific ERα Knockout Does Not Impact Hepatic Mitochondrial Function.Journal of the Endocrine Society · 2023Article
- Autophagy impairment in human bile duct carcinoma cells.Frontiers in physiology · 2023Article
- Cholangiokines: undervalued modulators in the hepatic microenvironment.Frontiers in immunology · 2023Review
- Mechanism of paracrine communications between hepatic progenitor cells and endothelial cells.Cellular signalling · 2022Article
- Characterization of the Estrogen Response Helps to Predict Prognosis and Identify Potential Therapeutic Targets in Cholangiocarcinoma.Frontiers in oncology · 2022Article
- Review of the literature on combined oral contraceptives and cancer.Ecancermedicalscience · 2022Review
- R-2HG downregulates ERα to inhibit cholangiocarcinoma via the FTO/m6A-methylated ERα/miR16-5p/YAP1 signal pathway.Molecular therapy oncolytics · 2021Article
- New insights on the role of vascular endothelial growth factor in biliary pathophysiology.JHEP reports : innovation in hepatology · 2021Review
- Recent Advances in the Mechanism Research and Clinical Treatment of Anti-Angiogenesis in Biliary Tract Cancer.Frontiers in oncology · 2021Review
- Anticancer Activity of Fucoidan via Apoptosis and Cell Cycle Arrest on Cholangiocarcinoma Cell.Asian Pacific journal of cancer prevention : APJCP · 2021Article
- Molecular and Immunohistochemical Analysis of Mucinous Cystic Neoplasm of the Liver.American journal of clinical pathology · 2020Article
- Associations Between Prediagnostic Concentrations of Circulating Sex Steroid Hormones and Liver Cancer Among Postmenopausal Women.Hepatology (Baltimore, Md.) · 2020Article
Corrections and comments
- Commented on by
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundEstrogens may induce the proliferation of neoplastic cells by activating neo-angiogenesis.
aimTo evaluate the effect of estrogens on the expression of vascular endothelial growth factor (VEGF) and related receptors (VEGF-R) in human cholangiocarcinoma and the role played by VEGF in mediating the proliferative effects of estrogens.
methodsSeven biopsies of intra-hepatic cholangiocarcinoma and the HuH-28 cell lines were investigated. Cell proliferation was measured by both PCNA Western blot and MTS proliferation assay.
resultsBy immunohistochemistry, biopsies of human cholangiocarcinoma stained positively for VEGF-A and VEGF-C and related receptors. HuH-28 cells expressed VEGF-A, -C, and VEGFR-1, -2, -3 and, their protein level was enhanced by 17beta-estradiol in association with the stimulation of cell proliferation. 17beta-Estradiol-stimulated proliferation of HuH-28 cells was blocked by 70% by VEGF-TRAP, a receptor-based VEGF inhibitor. 17beta-Estradiol induced the secretion of VEGF in the supernatant of HuH-28 cells. The stimulatory effect of 17beta-estradiol on the protein expression of VEGF-A, VEGF-C and VEGFR-1, -2, -3 was blocked by antagonists of ER (Ici182,780) or insulin-like growth factor 1-receptor (alphaIR3).
conclusionsWith the limitations of experiments performed in a cell line, our study indicates that VEGF plays a major role in mediating the proliferative effects of estrogens on human cholangiocarcinoma.
Indexed as
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.