Histamine H4 receptor as a novel therapeutic target for the treatment of Leydig-cell tumours in prepubertal boys

Abiuso, Adriana María Belén; Varela, Maria L.; Durand, Luis; Moreno, Marcos Alberto Besio; Marcos, Alejandra; Ponzio, Roberto; Rivarola, Marco A.; Belgorosky, Alicia; Pignataro, Omar Pedro; Berensztein, Esperanza; Mondillo, Carolina

doi:10.1016/j.ejca.2017.12.003

Cited by 8 publications

(10 citation statements)

References 31 publications

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“…Last but not least, a recent work in Leydig-cell tumors (LCT), which are rare testicular endocrine tumors shows that H4R agonist VUF8430 treatment inhibited steroidogenesis and proliferation in R2C cells and also reduced pro-angiogenic capacity both in vitro and in vivo . Furthermore, H4R immunostaining was weak in LCT but moderate/strong in normal prepubertal testes (Abiuso et al, 2014, 2018).…”

Section: H4r Expression In Melanoma and Other Cancersmentioning

confidence: 96%

Pathophysiological Role of Histamine H4 Receptor in Cancer: Therapeutic Implications

2019

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Cancer is a leading cause of death in both developed and developing countries. Although advances in cancer research lead to improved anti-neoplastic therapies, they continue to have unfavorable outcomes, including poor response and severe toxicity. Thus, the challenge for the new therapeutic approaches is to increase anti-tumor efficacy by targeting different molecules encompassed in the tumor and its microenvironment, as well as their specific interactions. The histamine H4 receptor (H4R) is the last discovered histamine receptor subtype and it modulates important immune functions in innate and in adaptive immune responses. Several ligands have been developed and some of them are being used in clinical trials for immune disorders with promising results. When searched in The Cancer Genome Atlas (TCGA) database, human H4R gene was found to be expressed in bladder cancer, kidney cancer, breast cancer, gastrointestinal cancers, lung cancer, endometrial cancer, and skin cancer. In the present work, we aimed to briefly summarize current knowledge in H4R’s pharmacology and in the clinical use of H4R ligands before focusing on recent data reporting the expression of H4R and its pathophysiological role in cancer, representing a potential molecular target for cancer therapeutics. H4R gene and protein expression in different types of cancers compared with normal tissue as well as its relationship with patient prognosis in terms of survival will be described.

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Section: H4r Expression In Melanoma and Other Cancersmentioning

confidence: 96%

Pathophysiological Role of Histamine H4 Receptor in Cancer: Therapeutic Implications

2019

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“…Abiuso et al, in their study, tested the ability of histamine receptor H4 agonist 2-(2-guanidinoethyl)isothiourea to negatively affect the pro-angiogenic effect of R2C rat Leydig tumour cell-derived conditioned medium applied on the CAM surface on the film discs [96]. The angiogenic activity of conditioned medium from senescent adipose-derived mesenchymal stem cells on vascularization of the quail CAM was studied by Ratushnyy et al [97].…”

Section: Angiogenesis Researchmentioning

confidence: 99%

“…Unlike in the chick CAM model, the smaller size of the quail CAM limits the application of multiple experimental substances. On the quail CAM model, Abiuso et al placed three film discs on one CAM simultaneously [96], while the chick CAM is large enough for application of up to six different samples [124,147]. Among the disadvantages of using quail for CAM assay is a more fragile constitution of the embryo and mottled pigmentation of Japanese quail eggshells, which make it difficult to stage the eggs by the candling method [124,149].…”

Section: Differences In Cam Assays Of Various Avian Speciesmentioning

confidence: 99%

Section: Differences In Cam Assays Of Various Avian Speciesmentioning

confidence: 99%

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Chorioallantoic Membrane Models of Various Avian Species: Differences and Applications

Kundeková

Máčajová

Meta

et al. 2021

Biology

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The chorioallantoic membrane model (CAM) of an avian embryo is used as an experimental model in various fields of research, including angiogenesis research and drug testing, xenografting and cancer research, and other scientific and commercial disciplines in microbiology, biochemistry, cosmetics, etc. It is a low-cost, low-maintenance, and well-available in vivo animal model that is non-sentient and can be used as an alternative for other mammal experimental models. It respects the principles of the “3R” rule (Replacement, Reduction, and Refinement)—conditions set out for scientific community providing an essential framework for conducting a more human animal research, which is also in line with constantly raising public awareness of welfare and the ethics related to the use of animal experimental models. In this review, we describe the chorioallantoic membrane of an avian embryo, focusing on its properties and development, its advantages and disadvantages as an experimental model, and the possibilities of its application in various fields of biological research. Since the most common chicken CAM model is already well known and described in many publications, we are particularly focusing on the advantages and application of less known avian species that are used for the CAM model—quail, turkey, and duck.

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“…The aim of this study was to implement a modern, live cell-based assay to study the molecular signaling mechanisms of putative histamine receptor agonists and antagonists. Moreover, the method needed to provide a proximal readout with improved signal amplitudes, which was essential for the weakly expressed H 4 R [28]. For these purposes, the mini-G protein concept was considered suitable.…”

Section: Introductionmentioning

confidence: 99%

A Dynamic, Split-Luciferase-Based Mini-G Protein Sensor to Functionally Characterize Ligands at All Four Histamine Receptor Subtypes

Höring

Seibel

Tropmann

et al. 2020

IJMS

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In drug discovery, assays with proximal readout are of great importance to study target-specific effects of potential drug candidates. In the field of G protein-coupled receptors (GPCRs), the determination of GPCR-G protein interactions and G protein activation by means of radiolabeled GTP analogs ([35S]GTPγS, [γ-32P]GTP) has widely been used for this purpose. Since we were repeatedly faced with insufficient quality of radiolabeled nucleotides, there was a requirement to implement a novel proximal functional assay for the routine characterization of putative histamine receptor ligands. We applied the split-NanoLuc to the four histamine receptor subtypes (H1R, H2R, H3R, H4R) and recently engineered minimal G (mini-G) proteins. Using this method, the functional response upon receptor activation was monitored in real-time and the four mini-G sensors were evaluated by investigating selected standard (inverse) agonists and antagonists. All potencies and efficacies of the studied ligands were in concordance with literature data. Further, we demonstrated a significant positive correlation of the signal amplitude and the mini-G protein expression level in the case of the H2R, but not for the H1R or the H3R. The pEC50 values of histamine obtained under different mini-G expression levels were consistent. Moreover, we obtained excellent dynamic ranges (Z’ factor) and the signal spans were improved for all receptor subtypes in comparison to the previously performed [35S]GTPγS binding assay.

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Histamine H4 receptor as a novel therapeutic target for the treatment of Leydig-cell tumours in prepubertal boys

Cited by 8 publications

References 31 publications

Pathophysiological Role of Histamine H4 Receptor in Cancer: Therapeutic Implications

Pathophysiological Role of Histamine H4 Receptor in Cancer: Therapeutic Implications

Chorioallantoic Membrane Models of Various Avian Species: Differences and Applications

A Dynamic, Split-Luciferase-Based Mini-G Protein Sensor to Functionally Characterize Ligands at All Four Histamine Receptor Subtypes

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