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

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Leydig-cell tumours (LCTs) are rare endocrine tumours of the testicular interstitium, with recent increased incidence. Symptoms include precocious puberty in children; and erectile dysfunction, infertility and/or gynaecomastia, in adults. So far, scientific evidence points to aromatase (CYP19) overe...

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Autor principal: Abiuso, A.M.B
Otros Autores: Varela, M.L, Haro Durand, L., Besio Moreno, M., Marcos, A., Ponzio, R., Rivarola, M.A, Belgorosky, A., Pignataro, O.P, Berensztein, E., Mondillo, C.
Formato: Capítulo de libro
Lenguaje:Inglés
Publicado: Elsevier Ltd 2018
Acceso en línea:Registro en Scopus
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024 7 |2 scopus  |a 2-s2.0-85041489521 
024 7 |2 cas  |a histamine H4 receptor, 272100-58-0; aromatase, 9039-48-9; clobenpropit, 145231-45-4; thiourea, 62-56-6; Angiogenesis Inhibitors; Antineoplastic Agents; AR protein, human; Aromatase; clobenpropit; CYP19A1 protein, human; ESR2 protein, human; Estrogen Receptor alpha; estrogen receptor alpha, human; Estrogen Receptor beta; Guanidines; Histamine Agonists; IGF1R protein, human; Imidazoles; Receptors, Androgen; Receptors, Histamine H4; Receptors, Somatomedin; S-(2-guanidylethyl)isothiourea; Steroid Synthesis Inhibitors; Thiourea 
040 |a Scopus  |b spa  |c AR-BaUEN  |d AR-BaUEN 
030 |a EJCAE 
100 1 |a Abiuso, A.M.B. 
245 1 0 |a Histamine H4 receptor as a novel therapeutic target for the treatment of Leydig-cell tumours in prepubertal boys 
260 |b Elsevier Ltd  |c 2018 
270 1 0 |m Mondillo, C.; Laboratorio de Endocrinología Molecular y Transducción de Señales, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Vuelta de Obligado 2490, Argentina; email: carolina.mondillo@gmail.com 
506 |2 openaire  |e Política editorial 
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504 |a Lanzafame, S., Leonardi, R., Torrisi, A., Extratesticular Leydig cell tumor of the spermatic cord (2004) J Urol, 171, pp. 1238-1239 
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504 |a Abiuso, A.M., Berensztein, E., Pagotto, R.M., Pereyra, E.N., Medina, V., Martinel Lamas, D.J., Besio Moreno, M., Mondillo, C., H4 histamine receptors inhibit steroidogenesis and proliferation in Leydig cells (2014) J Endocrinol, 223, pp. 241-253 
504 |a Haro Durand, L., Góngora, A., Porto López, J.M., Boccaccini, A., Zago, M.P., Baldi, A., In vitro endothelial cell response to ionic dissolution products from a boron-doped bioactive glass in the SiO2–CaO–P2O5–Na2O system (2014) J Mater Chem B, 2, pp. 7620-7630 
504 |a Parsons-Wingerter, P., Lwai, B., Yang, M.C., Elliot, K.E., Milaninia, A., Redlitz, A., A novel assay of angiogenesis in the quail chorioallantoic membrane: stimulation by bFGF and inhibition by angiostatin according to fractal dimension and grid intersection (1998) Microvasc Res, 55, pp. 201-214 
504 |a Vargas, G., Haro Durand, L., Cadena, V., Romero, M., Mesones, R.V., Mackovic, M., Effect of nano-sized bioactive glass particles on the angiogenic properties of collagen based composites (2013) J Mater Sci Mater Med, 24, pp. 1261-1269 
504 |a Berensztein, E.B., Baquedano, M.S., Gonzalez, C.R., Saraco, N.I., Rodriguez, J., Ponzio, R., Expression of aromatase, estrogen receptor alpha and beta, androgen receptor, and cytochrome P-450scc in the human early prepubertal testis (2006) Pediatr Res, 60, pp. 740-744 
504 |a Berensztein, E.B., Baquedano, M.S., Pepe, C.M., Costanzo, M., Saraco, N.I., Ponzio, R., Role of IGFs and insulin in the human testis during postnatal activation: differentiation of steroidogenic cells (2008) Pediat Res, 63, pp. 662-666 
504 |a Garcia-Caballero, M., Neugebauer, E., Rodriguez, F., Nuñez de Castro, I., Vara-Thorbeck, C., Histamine synthesis and content in benign and malignant breast tumours. Its effects on other host tissues (1994) Surg Oncol, 3, pp. 167-173 
504 |a Reynolds, J.L., Akhter, J., Adams, W.J., Morris, D.L., Histamine content in colorectal cancer. Are there sufficient levels of histamine to affect lymphocyte function? (1997) Eur J Surg Oncol, 23, pp. 224-227 
504 |a Hegyesi, H., Somlai, B., Varga, V.L., Toth, G., Kovacs, P., Molnar, E.L., Suppression of melanoma cell proliferation by histidine decarboxylase specific antisense oligonucleotides (2001) J Invest Dermatol, 117, pp. 151-153 
504 |a Sieja, K., Stanosz, S., von Mach-Szczypiński, J., Olewniczak, S., Stanosz, M., Concentration of histamine in serum and tissues of the primary ductal breast cancers in women (2005) Breast, 14, pp. 236-241 
504 |a von Mach-Szczypiński, J., Stanosz, S., Sieja, K., Stanosz, M., Histamine and its metabolizing enzymes in tissues of primary ductal breast cancer (2009) Eur J Gynaecol Oncol, 30, pp. 509-511 
504 |a Abiuso, A., Marcos, A., Belgorosky, A., Rivarola, M., Besio Moreno, M., Pignataro, O., Histidine Decarboxylase: a novel therapeutic target for the treatment of Leydig cell tumors? Endocrine Society's 98th annual meeting and expo, April 1–4 2016 – Boston, MA, United States of America; Pagotto, R.M., Monzon, C., Moreno, M.B., Pignataro, O.P., Mondillo, C., Proliferative effect of histamine on MA-10 Leydig tumor cells mediated through HRH2 activation, transient elevation in cAMP production, and increased extracellular signal-regulated kinase phosphorylation levels (2012) Biol Reprod, 87, p. 150 
504 |a Fang, Z., Yao, W., Xiong, Y., Li, J., Liu, L., Shi, L., Attenuated expression of HRH4 in colorectal carcinomas: a potential influence on tumor growth and progression (2011) BMC Cancer, 11, pp. 1-11 
504 |a Zhang, C., Xiong, Y., Li, J., Yang, Y., Liu, L., Wang, W., Deletion and down-regulation of HRH4 gene in gastric carcinomas: a potential correlation with tumor progression (2012) PLoS One, 7 
504 |a Nguyen, T., Shapiro, D., George, S., Steola, V., Lee, D., Cheng, R., Discovery of a novel member of the histamine receptor family (2001) Mol Pharmacol, 59, pp. 427-433 
504 |a Petit-Bertron, A.F., Machavoine, F., Defresne, M.P., Gillard, M., Chatelain, P., Mistry, P., H4 histamine receptors mediate cell cycle arrest in growth factor-induced murine and human hematopoietic progenitor cells (2009) PLoS One, 4 
504 |a Manna, P.R., Dyson, M.T., Eubank, D.W., Clark, B.J., Lalli, E., Sassone-Corsi, P., Regulation of steroidogenesis and the steroidogenic acute regulatory protein by a member of the cAMP response-element binding protein family (2002) Mol Endocrinol, 16, pp. 184-199 
504 |a Meng, F., Han, Y., Staloch, D., Francis, T., Stokes, A., Francis, H., The H4 histamine receptor agonist, clobenpropit, suppresses human cholangiocarcinoma progression by disruption of epithelial mesenchymal transition and tumor metastasis (2011) Hepatology, 54, pp. 1718-1728 
504 |a Paik, W.H., Ryu, J.K., Jeong, K.S., Park, J.M., Song, B.J., Lee, S.H., Clobenpropit enhances anti-tumor effect of gemcitabine in pancreatic cancer (2014) World J Gastroenterol, 20, pp. 8545-8557 
504 |a Qin, L., Zhao, D., Xu, J., Ren, X., Terwilliger, E.F., Parangi, S., The vascular permeabilizing factors histamine and serotonin induce angiogenesis through TR3/Nur77 and subsequently truncate it through thrombospondin-1 (2013) Blood, 121, pp. 2154-2164 
504 |a Krusche, B., Arend, J., Efferth, T., Synergistic inhibition of angiogenesis by artesunate and captopril in vitro and in vivo (2013) Evid Based Complement Alternat Med, 2013 
504 |a Schwarzenbach, H., Chakrabarti, G., Paust, H.J., Mukhopadhyay, A.K., Gonadotropin-mediated regulation of the murine VEGF expression in MA-10 Leydig cells (2004) J Androl, 25, pp. 128-139 
504 |a Maizlin, Z.V., Belenky, A., Kunichezky, M., Sandbank, J., Strauss, S., Leydig cell tumors of the testis: gray scale and color Doppler sonographic appearance (2004) J Ultrasound Med, 23, pp. 959-964 
504 |a Shenker, A., Laue, L., Kosugi, S., Merendino, J.J., Jr., Minegishi, T., Cutler, G.B., Jr., A constitutively activating mutation of the luteinizing hormone receptor in familial male precocious puberty (1993) Nature, 365, pp. 652-654 
504 |a Maris, P., Campana, A., Barone, I., Giordano, C., Morelli, C., Malivindi, R., Androgens inhibit aromatase expression through DAX-1: insights into the molecular link between hormone balance and Leydig cancer development (2015) Endocrinology, 156, pp. 1251-1262 
504 |a Allred, D.C., Bustamante, M.A., Daniel, C.O., Gaskill, H.V., Cruz, A.B., Jr., Immunocytochemical analysis of estrogen receptors in human breast carcinomas. Evaluation of 130 cases and review of the literature regarding concordance with biochemical assay and clinical relevance (1990) Arch Surg, 125, pp. 107-113 
520 3 |a Leydig-cell tumours (LCTs) are rare endocrine tumours of the testicular interstitium, with recent increased incidence. Symptoms include precocious puberty in children; and erectile dysfunction, infertility and/or gynaecomastia, in adults. So far, scientific evidence points to aromatase (CYP19) overexpression and excessive oestrogen and insulin-like growth factor (IGF) –1 production as responsible for Leydig-cell tumourigenesis. LCTs are usually benign; however, malignant LCTs respond poorly to chemo/radiotherapy, highlighting the need to identify novel targets for treatment. Herein, we investigated the potential role of the histamine receptor H4 (HRH4) as a therapeutic target for LCTs using R2C rat Leydig tumour cells, a well-documented in vitro model for Leydigioma. Also, we studied for the first time the expression of CYP19, IGF-1R, oestrogen receptor (ER) α ERβ androgen receptor (AR) and HRH4 in human prepubertal LCTs versus normal prepubertal testes (NPTs). HRH4 agonist treatment inhibited steroidogenesis and proliferation in R2C cells and also negatively affected their pro-angiogenic capacity in vitro and in vivo, as assessed by evaluating the proliferative activity of human umbilical vein endothelial cells and by means of the quail chorioallantoic membrane assay, respectively. Moreover, E2 and IGF-1 inhibited HRH4 mRNA and protein levels. In human prepubertal LCTs, CYP19, IGF-1R, ERα and ERβ were overexpressed compared with NPTs. In contrast, HRH4 staining was weak in LCTs, but moderate/strong and confined to the interstitium in NPTs. Importantly, HRH4 was absent or barely detectable in seminiferous tubules or germ cells. Overall, our results point to HRH4 as a novel therapeutic target in LCTs. © 2017 Elsevier Ltd  |l eng 
536 |a Detalles de la financiación: Universidad de Buenos Aires, UBACYT 2013-20020120100205 
536 |a Detalles de la financiación: Agencia Nacional de Promoción Científica y Tecnológica, PICT 2015 N° 2650, PICT 2012 N° 2776 
536 |a Detalles de la financiación: Consejo Nacional de Investigaciones Científicas y Técnicas, PIP 392 
536 |a Detalles de la financiación: Fundación Alberto J. Roemmers 
536 |a Detalles de la financiación: Office of Polar Programs 
536 |a Detalles de la financiación: Fundación René Barón 
536 |a Detalles de la financiación: This investigation was supported by grants from the Agencia Nacional de Promoción Científica y Tecnológica (ANPCYT, PICT 2012 N° 2776 and PICT 2015 N° 2650 ), the Alberto J. Roemmers Foundation to CM, the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET, PIP 392 ) and the University of Buenos Aires (UBA, UBACYT 2013-20020120100205 ) to OPP. 
536 |a Detalles de la financiación: Financial support was also given by Fundación Williams and Fundación René Barón . Appendix A 
593 |a Laboratorio de Endocrinología Molecular y Transducción de Señales, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Vuelta de Obligado 2490, Buenos Aires, C1428ADN, Argentina 
593 |a Laboratorio de Patología y Farmacología Molecular, IBYME-CONICET, Buenos Aires, Argentina 
593 |a Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina 
593 |a Servicio de Endocrinología, Hospital de Pediatría “Prof. Dr.Juan P. Garrahan”, Buenos Aires, Argentina 
593 |a Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina 
690 1 0 |a ANGIOGENESIS 
690 1 0 |a CYP19 AROMATASE 
690 1 0 |a HISTAMINE 
690 1 0 |a HISTAMINE RECEPTOR H4 
690 1 0 |a LEYDIG-CELL TUMOUR 
690 1 0 |a OESTRADIOL 
690 1 0 |a STEROIDOGENESIS 
690 1 0 |a ANDROGEN RECEPTOR 
690 1 0 |a CYTOCHROME P450 FAMILY 19 
690 1 0 |a ESTROGEN RECEPTOR ALPHA 
690 1 0 |a ESTROGEN RECEPTOR BETA 
690 1 0 |a HISTAMINE H4 RECEPTOR 
690 1 0 |a SOMATOMEDIN C RECEPTOR 
690 1 0 |a ANDROGEN RECEPTOR 
690 1 0 |a ANGIOGENESIS INHIBITOR 
690 1 0 |a ANTINEOPLASTIC AGENT 
690 1 0 |a AR PROTEIN, HUMAN 
690 1 0 |a AROMATASE 
690 1 0 |a CLOBENPROPIT 
690 1 0 |a CYP19A1 PROTEIN, HUMAN 
690 1 0 |a ESR2 PROTEIN, HUMAN 
690 1 0 |a ESTROGEN RECEPTOR ALPHA 
690 1 0 |a ESTROGEN RECEPTOR ALPHA, HUMAN 
690 1 0 |a ESTROGEN RECEPTOR BETA 
690 1 0 |a GUANIDINE DERIVATIVE 
690 1 0 |a HISTAMINE AGONIST 
690 1 0 |a HISTAMINE H4 RECEPTOR 
690 1 0 |a IGF1R PROTEIN, HUMAN 
690 1 0 |a IMIDAZOLE DERIVATIVE 
690 1 0 |a S-(2-GUANIDYLETHYL)ISOTHIOUREA 
690 1 0 |a SOMATOMEDIN RECEPTOR 
690 1 0 |a STEROID SYNTHESIS INHIBITOR 
690 1 0 |a THIOUREA 
690 1 0 |a ANGIOGENESIS 
690 1 0 |a ANIMAL CELL 
690 1 0 |a ANIMAL CELL CULTURE 
690 1 0 |a ANIMAL EXPERIMENT 
690 1 0 |a ANIMAL MODEL 
690 1 0 |a ARTICLE 
690 1 0 |a CELL PROLIFERATION 
690 1 0 |a CELL PROLIFERATION ASSAY 
690 1 0 |a CHORIOALLANTOIC MEMBRANE ASSAY 
690 1 0 |a CONTROLLED STUDY 
690 1 0 |a DRUG TARGETING 
690 1 0 |a HUMAN 
690 1 0 |a HUMAN CELL 
690 1 0 |a HUMAN TISSUE 
690 1 0 |a IMMUNOHISTOCHEMISTRY 
690 1 0 |a IN VITRO STUDY 
690 1 0 |a IN VIVO STUDY 
690 1 0 |a LEYDIG CELL TUMOR 
690 1 0 |a MALE 
690 1 0 |a NONHUMAN 
690 1 0 |a PREPUBERTY 
690 1 0 |a PRIORITY JOURNAL 
690 1 0 |a PROTEIN EXPRESSION 
690 1 0 |a R2C CELL LINE 
690 1 0 |a RAT 
690 1 0 |a REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION 
690 1 0 |a STEROIDOGENESIS 
690 1 0 |a TESTIS TISSUE 
690 1 0 |a TUMOR CELL 
690 1 0 |a UMBILICAL VEIN ENDOTHELIAL CELL 
690 1 0 |a WESTERN BLOTTING 
690 1 0 |a AGE 
690 1 0 |a AGONISTS 
690 1 0 |a ANALOGS AND DERIVATIVES 
690 1 0 |a ANIMAL 
690 1 0 |a COTURNIX 
690 1 0 |a DRUG EFFECT 
690 1 0 |a EMBRYOLOGY 
690 1 0 |a INFANT 
690 1 0 |a LEYDIG CELL TUMOR 
690 1 0 |a METABOLISM 
690 1 0 |a MOLECULARLY TARGETED THERAPY 
690 1 0 |a NEOVASCULARIZATION (PATHOLOGY) 
690 1 0 |a PATHOLOGY 
690 1 0 |a SIGNAL TRANSDUCTION 
690 1 0 |a TESTIS TUMOR 
690 1 0 |a TUMOR CELL LINE 
690 1 0 |a AGE FACTORS 
690 1 0 |a ANGIOGENESIS INHIBITORS 
690 1 0 |a ANIMALS 
690 1 0 |a ANTINEOPLASTIC AGENTS 
690 1 0 |a AROMATASE 
690 1 0 |a CELL LINE, TUMOR 
690 1 0 |a CELL PROLIFERATION 
690 1 0 |a COTURNIX 
690 1 0 |a ESTROGEN RECEPTOR ALPHA 
690 1 0 |a ESTROGEN RECEPTOR BETA 
690 1 0 |a GUANIDINES 
690 1 0 |a HISTAMINE AGONISTS 
690 1 0 |a HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS 
690 1 0 |a HUMANS 
690 1 0 |a IMIDAZOLES 
690 1 0 |a INFANT 
690 1 0 |a LEYDIG CELL TUMOR 
690 1 0 |a MALE 
690 1 0 |a MOLECULAR TARGETED THERAPY 
690 1 0 |a NEOVASCULARIZATION, PATHOLOGIC 
690 1 0 |a RATS 
690 1 0 |a RECEPTORS, ANDROGEN 
690 1 0 |a RECEPTORS, HISTAMINE H4 
690 1 0 |a RECEPTORS, SOMATOMEDIN 
690 1 0 |a SIGNAL TRANSDUCTION 
690 1 0 |a STEROID SYNTHESIS INHIBITORS 
690 1 0 |a TESTICULAR NEOPLASMS 
690 1 0 |a THIOUREA 
700 1 |a Varela, M.L. 
700 1 |a Haro Durand, L. 
700 1 |a Besio Moreno, M. 
700 1 |a Marcos, A. 
700 1 |a Ponzio, R. 
700 1 |a Rivarola, M.A. 
700 1 |a Belgorosky, A. 
700 1 |a Pignataro, O.P. 
700 1 |a Berensztein, E. 
700 1 |a Mondillo, C. 
773 0 |d Elsevier Ltd, 2018  |g v. 91  |h pp. 125-135  |p Eur. J. Cancer  |x 09598049  |w (AR-BaUEN)CENRE-4655  |t European Journal of Cancer 
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856 4 0 |u https://doi.org/10.1016/j.ejca.2017.12.003  |y DOI 
856 4 0 |u https://hdl.handle.net/20.500.12110/paper_09598049_v91_n_p125_Abiuso  |y Handle 
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