NOTCH signalling in ovarian cancer angiogenesis

Pérez-Fidalgo, José Alejandro; Ortega, Belén; Simón, Soraya; Samartzis, Eleftherios Pierre; Boussios, Stergios

doi:10.21037/atm-20-4497

Cited by 34 publications

(25 citation statements)

References 71 publications

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“…For example, C10orf55 has been found to be a potential biomarker to predict the relapse of acute myeloid leukemia (18). DLL4 plays a key role in tumor angiogenesis, functioning as a negative regulator of tumor angiogenesis and is upregulated in the tumor vasculature (19,20). A previous study indicated that DLL4 could be an independent prognostic factor for predicting the OS of patients with non-small cell lung cancer and was correlated with immunocyte infiltration (21).…”

Section: Discussionmentioning

confidence: 99%

Development of a novel miR-3648-related gene signature as a prognostic biomarker in esophageal adenocarcinoma

Zhang¹,

Yin²,

Bauer³

et al. 2021

Ann Transl Med

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Background: Esophageal adenocarcinoma (EA) is a typical immunogenic malignant tumor with a dismal 5-year survival rate lower than 20%. Although miRNA-3648 (miR-3648) is expressed abnormally in EA, its impact on the tumor immune microenvironment remains unknown. In this study, we sought to identify immune-related genes (IRGs) that are targeted by miR-3648 and develop an EA multigene signature. Methods:The gene expression data of 87 EA tumor samples and 67 normal tissue samples from The Cancer Genome Atlas (TCGA) database and the Genotype-Tissue Expression (GTEx) database were downloaded, respectively. Weighted gene co-expression network analysis (WGCNA), the CIBERSORT algorithm, and Cox regression analysis were applied to identify IRGs and to construct a prognostic signature and nomogram.Results: MiR-3648 was expectedly highly expressed in EA tumor tissues (P=2.6e-8), and related to the infiltration of activated natural killer cells (NK cells) and activated CD4 T lymphocytes (CD4 cells). A total of 70 miR-3648-targeted genes related to immune cell infiltration were identified. Among them, 4 genes (C10orf55, DLL4, PANX2, and NKAIN1) were closely related to overall survival (OS), and were thus selected to construct a 4-gene risk score (RS). The RS had a superior capability to predict OS [area under the curve (AUC) =0.740 for 1 year; AUC =0.717 for 3 years; AUC =0.622 for 5 years]. A higher score was indicative of a poorer prognosis than a lower score [hazard ratio (HR) =2.71; 95% confidence interval (CI): 1.45-5.09; P=0.002]. Furthermore, the nomogram formed by combining the RS and the TNM classification of malignant tumors (TNM stage) improved the accuracy of survival prediction [Harrell's concordance index (C-index) =0.698].Conclusions: MiR-3648 may play a critical role in EA pathogenesis. The novel 4-gene signature may serve as a prognostic tool to manage patients with EA.

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Section: Discussionmentioning

confidence: 99%

Development of a novel miR-3648-related gene signature as a prognostic biomarker in esophageal adenocarcinoma

Zhang¹,

Yin²,

Bauer³

et al. 2021

Ann Transl Med

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“…Then, navicixizumab had been further investigated in combination with paclitaxel in platinum-resistant ovarian cancer patients in a Phase 1b study (NCT03030287). By 2020, 44 patients had been included and the overall response rate (ORR) of this combination was 43% including 1 CR and 18 PR [ 118 ].…”

Section: Targeting Antigensmentioning

confidence: 99%

Recent advances and challenges of bispecific antibodies in solid tumors

Zhu

et al. 2021

Exp Hematol Oncol

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Cancer immunotherapy has made remarkable progress in the past decade. Bispecific antibodies (BsAbs) have acquired much attention as the next generation strategy of antibody-target cancer immunotherapy, which overwhelmingly focus on T cell recruitment and dual receptors blockade. So far, BsAb drugs have been proved clinically effective and approved for the treatment of hematologic malignancies, but no BsAb have been approved in solid tumors. Numerous designed BsAb drugs for solid tumors are now undergoing evaluation in clinical trials. In this review, we will introduce the formats of bispecific antibodies, and then update the latest preclinical studies and clinical trials in solid tumors of BsAbs targeting EpCAM, CEA, PMSA, ErbB family, and so on. Finally, we discuss the BsAb-related adverse effects and the alternative strategy for future study.

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“…Notch signalling is detected in the early stages of pancreatic development, where it directs the recruitment of endocrine cells from their progenitor cells, but many studies also indicate that its function extends to exocrine development [42]. Notch signalling has been implicated in several human pathologies of cardiovascular origin as well as in numerous cancers [43][44][45][46].…”

Section: Notch Signallingmentioning

confidence: 99%

The TWEAK/Fn14/CD163 axis—implications for metabolic disease

Ratajczak

Atkinson

Kelly

2021

Rev Endocr Metab Disord

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TWEAK (tumor necrosis factor-like weak inducer of apoptosis) is a member of the TNF superfamily that controls a multitude of cellular events including proliferation, migration, differentiation, apoptosis, angiogenesis, and inflammation. TWEAK control of these events is via an expanding list of intracellular signalling pathways which include NF-κB, ERK/MAPK, Notch, EGFR and AP-1. Two receptors have been identified for TWEAK – Fn14, which targets the membrane bound form of TWEAK, and CD163, which scavenges the soluble form of TWEAK. TWEAK appears to elicit specific events based on the receptor to which it binds, tissue type in which it is expressed, specific extrinsic conditions, and the presence of other cytokines. TWEAK signalling is protective in healthy tissues, but in chronic inflammatory states become detrimental to the tissue. Consistent data show a role for the TWEAK/FN14/CD163 axis in metabolic disease, chronic autoimmune diseases, and acute ischaemic stroke. Low circulating concentrations of soluble TWEAK are predictive of poor cardiovascular outcomes in those with and without diabetes. This review details the current understanding of the TWEAK/Fn14/CD163 axis as one of the chief regulators of immune signalling and its cell-specific role in metabolic disease development and progression.

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NOTCH signalling in ovarian cancer angiogenesis

Cited by 34 publications

References 71 publications

Development of a novel miR-3648-related gene signature as a prognostic biomarker in esophageal adenocarcinoma

Development of a novel miR-3648-related gene signature as a prognostic biomarker in esophageal adenocarcinoma

Recent advances and challenges of bispecific antibodies in solid tumors

The TWEAK/Fn14/CD163 axis—implications for metabolic disease

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