ArticleWorld journal of gastroenterology2011
Clinicopathological significance of altered Notch signaling in extrahepatic cholangiocarcinoma and gallbladder carcinoma.
Article in World journal of gastroenterology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 43 citations in OpenAlex.
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- COMPANION-002 A clinical trial of investigational drug CTX-009 plus paclitaxel vs paclitaxel in second line advanced BTC.Future oncology (London, England) · 2024Article
- Globo H ceramide is an independent prognostic marker for gallbladder cancer.American journal of cancer research · 2023Article
- Implication of Ferroptosis in Cholangiocarcinoma: A Potential Future Target?Cancer management and research · 2023Review
- Notch Signaling Pathway in Pancreatobiliary Tumors.Medicina (Kaunas, Lithuania) · 2021Article
- Targeting gallbladder cancer: a pathway based perspective.Molecular biology reports · 2020Review
- The Role of DLLs in Cancer: A Novel Therapeutic Target.OncoTargets and therapy · 2020Review
- MPZL1 is highly expressed in advanced gallbladder carcinoma and promotes the aggressive behavior of human gallbladder carcinoma GBC‑SD cells.Molecular medicine reports · 2019Article
- Molecular Pathogenesis of Cholangiocarcinoma.BMC cancer · 2019Review
- Gallbladder cancer: review of a rare orphan gastrointestinal cancer with a focus on populations of New Mexico.BMC cancer · 2018Review
- KrasOncoscience · 2017Article
- Biliary cancer: intrahepatic cholangiocarcinomaJournal of gastrointestinal oncology · 2017Review
- Expression and prognostic value of glutamate dehydrogenase in extrahepatic cholangiocarcinoma patients.American journal of translational research · 2017Article
- Clinical implications of APEX1 and Jagged1 as chemoresistance factors in biliary tract cancer.Annals of surgical treatment and research · 2017Article
- Article
- MicroRNA-133a-3p exerts inhibitory effects on gallbladder carcinoma via targeting RBPJ.American journal of cancer research · 2016Article
- Characterization of Notch Signalling Pathway Members in Normal Prostate, Prostatic Intraepithelial Neoplasia (PIN) and Prostatic Adenocarcinoma.Pathology oncology research : POR · 2016Article
- Targeted Therapy in Biliary Tract Cancers.Current treatment options in oncology · 2015Review
- PGE2 signaling and its biosynthesis-related enzymes in cholangiocarcinoma progression.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- Clinicopathological significance of aberrant Notch receptors in intrahepatic cholangiocarcinoma.International journal of clinical and experimental pathology · 2014Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimTo investigate the role and clinicopathological significance of aberrant expression of Notch receptors and Delta-like ligand-4 (DLL4) in extrahepatic cholangiocarcinoma and gallbladder carcinoma.
methodsOne hundred and ten patients had surgically resected extrahepatic cholangiocarcinoma (CC) and gallbladder carcinoma specimens examined by immunohistochemistry of available paraffin blocks. Immunohistochemistry was performed using anti-Notch receptors 1-4 and anti-DLL4 antibodies. We scored the immunopositivity of Notch receptors and DLL4 expression by percentage of positive tumor cells with cytoplasmic expression and intensity of immunostaining. Coexistent nuclear localization was evaluated. Clinicopathological parameters and survival data were compared with the expression of Notch receptors 1-4 and DLL4.
resultsNotch receptor proteins showed in the cytoplasm with or without nuclear expression in cancer cells, as well as showing weak cytoplasmic expression in non-neoplastic cells. By semiquantitative evaluation, positive immunostaining of Notch receptor 1 was detected in 96 cases (87.3%), Notch receptor 2 in 97 (88.2%), Notch receptor 3 in 97 (88.2%), Notch receptor 4 in 103 (93.6), and DLL4 in 84 (76.4%). In addition, coexistent nuclear localization was noted [Notch receptor 1; 18 cases (18.8%), Notch receptor 2; 40 (41.2%), Notch receptor 3; 32 (33.0%), Notch receptor 4; 99 (96.1%), DLL4; 48 (57.1%)]. Notch receptor 1 expression was correlated with advanced tumor, node, metastasis (TNM) stage (P = 0.043), Notch receptor 3 with advanced T stage (P = 0.017), tendency to express in cases with nodal metastasis (P = 0.065) and advanced TNM stage (P = 0.052). DLL4 expression tended to be related to less histological differentiation (P = 0.095). Coexistent nuclear localization of Notch receptor 3 was related to no nodal metastasis (P = 0.027) and Notch receptor 4 with less histological differentiation (P = 0.036), while DLL4 tended to be related inversely with T stage (P = 0.053). Coexistent nuclear localization of DLL4 was related to poor survival (P = 0.002).
conclusionAberrant expression of Notch receptors 1 and 3 play a role during cancer progression, and cytoplasmic nuclear coexistence of DLL4 expression correlates with poor survival in extrahepatic CC and gallbladder carcinoma.
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