{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:19:09Z","timestamp":1760145549537,"version":"build-2065373602"},"reference-count":36,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T00:00:00Z","timestamp":1723593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund","award":["TKP2021-EGA","\u00daNKP-23-4-I-DE-157","OTKA K143021"],"award-info":[{"award-number":["TKP2021-EGA","\u00daNKP-23-4-I-DE-157","OTKA K143021"]}]},{"name":"National Research, Development and Innovation Fund and the Foundation for Children with Leukemia","award":["TKP2021-EGA","\u00daNKP-23-4-I-DE-157","OTKA K143021"],"award-info":[{"award-number":["TKP2021-EGA","\u00daNKP-23-4-I-DE-157","OTKA K143021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hematological and oncological diseases are still among the leading causes of childhood mortality. Expression of growth hormone-releasing hormone (GHRH) and its receptors (GHRH-R) has been previously demonstrated in various human tumors, but very limited findings are available about the presence and potential function of GHRH-Rs in oncological and hematological disorders of children. In this study, we aimed to investigate the expression of mRNA for GHRH and splice variant 1 (SV) of GHRH-R in 15 pediatric hematological\/oncological specimens by RT-PCR. The presence and binding characteristics of GHRH-R protein were also studied by Western blot and ligand competition assays. Of the fifteen specimens studied, eleven pediatric samples (73%) showed the expression of mRNA for GHRH. These eleven samples also expressed mRNA for GHRH receptor SV1. GHRH-R protein was found to be expressed in two benign tumor samples and five malignant tumors examined by Western blot. The presence of specific, high affinity binding sites on GHRH-R was demonstrated in all of the seven human pediatric solid tumor samples investigated. Our results show that the expression of GHRH and SV1 of GHRH-R in hemato-oncological diseases in children can pave the way for further investigation of GHRH-Rs as potential molecular targets for diagnosis and therapy.<\/jats:p>","DOI":"10.3390\/ijms25168831","type":"journal-article","created":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T05:23:27Z","timestamp":1723613007000},"page":"8831","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Expression of Growth Hormone-Releasing Hormone and Its Receptor Splice Variants in a Cohort of Hungarian Pediatric Patients with Hematological and Oncological Disorders: A Pilot Study"],"prefix":"10.3390","volume":"25","author":[{"given":"\u00c9va","family":"Juh\u00e1sz","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zsuzsanna","family":"Szab\u00f3","sequence":"additional","affiliation":[{"name":"Department of Biopharmacy, Faculty of Pharmacy, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew V.","family":"Schally","sequence":"additional","affiliation":[{"name":"Veterans Affairs Medical Center, Endocrine, Polypeptide and Cancer Institute, Miami, FL 33125, USA"},{"name":"Department of Pathology, Miller School of Medicine, University of Miami, Miami, FL 33101, USA"},{"name":"Department of Medicine, Divisions of Hematology-Oncology and Endocrinology, Miller School of Medicine, University of Miami, Miami, FL 33101, USA"},{"name":"Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f3zsef","family":"Kir\u00e1ly","sequence":"additional","affiliation":[{"name":"Department of Biopharmacy, Faculty of Pharmacy, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Fodor","sequence":"additional","affiliation":[{"name":"Department of Biopharmacy, Faculty of Pharmacy, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00e1bor","family":"K\u00f3nya","sequence":"additional","affiliation":[{"name":"Department of Biopharmacy, Faculty of Pharmacy, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bal\u00e1zs","family":"Dezs\u0151","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erzs\u00e9bet","family":"Szab\u00f3","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, HUN-REN-DE Pharmamodul Research Group, University of Debrecen, Nagyerdei krt. 98, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00e1bor","family":"Halmos","sequence":"additional","affiliation":[{"name":"Department of Biopharmacy, Faculty of Pharmacy, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"Veterans Affairs Medical Center, Endocrine, Polypeptide and Cancer Institute, Miami, FL 33125, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5170-5965","authenticated-orcid":false,"given":"Csongor","family":"Kiss","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,14]]},"reference":[{"key":"ref_1","first-page":"33","article-title":"Antagonists of growth-hormone-releasing hormone: An emerging new therapy for cancer. Nature clinical practice","volume":"4","author":"Schally","year":"2008","journal-title":"Endocrinol. Metab."},{"key":"ref_2","first-page":"1734","article-title":"Molecular cloning and expression of a pituitary-specific receptor for growth hormone-releasing hormone","volume":"6","author":"Mayo","year":"1992","journal-title":"Mol. Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1023\/A:1020949507265","article-title":"Growth Hormone Releasing Hormone (GHRH) and the GHRH Receptor","volume":"3","author":"Wajnrajch","year":"2002","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1006\/frne.2001.0217","article-title":"Hypothalamic hormones and cancer","volume":"22","author":"Schally","year":"2001","journal-title":"Front. Neuroendocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"V\u00e9lez, E.J., and Unniappan, S. (2020). A Comparative Update on the Neuroendocrine Regulation of Growth Hormone in Vertebrates. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.614981"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/nrendo.2018.22","article-title":"Growth hormone-past, present and future","volume":"14","author":"Ranke","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.vh.2023.06.004","article-title":"Signaling mechanism of growth hormone-releasing hormone receptor","volume":"123","author":"Halmos","year":"2023","journal-title":"Vitam. Horm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"56","DOI":"10.2174\/157489212798358010","article-title":"Antineoplastic action of growth hormone-releasing hormone (GHRH) antagonists","volume":"7","author":"Siejka","year":"2012","journal-title":"Recent. Pat. Anticancer Drug Discov."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6726","DOI":"10.1073\/pnas.1913433117","article-title":"Splice variant of growth hormone-releasing hormone receptor drives esophageal squamous cell carcinoma conferring a therapeutic target","volume":"117","author":"Xiong","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e2106606118","DOI":"10.1073\/pnas.2106606118","article-title":"Constitutive signal bias mediated by the human GHRHR splice variant 1","volume":"118","author":"Cong","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Szabo, Z., Juhasz, E., Schally, A.V., Dezso, B., Huga, S., Hernadi, Z., Halmos, G., and Kiss, C. (2022). Expression of Growth Hormone-Releasing Hormone and Its Receptor Splice Variants in Primary Human Endometrial Carcinomas: Novel Therapeutic Approaches. Molecules, 27.","DOI":"10.3390\/molecules27092671"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"10561","DOI":"10.1073\/pnas.180313297","article-title":"Isolation and sequencing of cDNAs for splice variants of growth hormone-releasing hormone receptors from human cancers","volume":"97","author":"Rekasi","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21708","article-title":"Cancer statistics, 2022","volume":"72","author":"Siegel","year":"2022","journal-title":"CA A Cancer J. Clin."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1093\/jnci\/djad115","article-title":"Counts, incidence rates, and trends of pediatric cancer in the United States, 2003\u20132019","volume":"115","author":"Siegel","year":"2023","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Agarwal, S. (2023). Pediatric Cancers: Insights and Novel Therapeutic Approaches. Cancers, 15.","DOI":"10.3390\/cancers15143537"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4218","DOI":"10.1002\/cncr.24465","article-title":"Trends in childhood rhabdomyosarcoma incidence and survival in the United States, 1975-2005","volume":"115","author":"Ognjanovic","year":"2009","journal-title":"Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S0165-5876(00)00288-3","article-title":"Nasopharyngeal teratomas and dermoids: A review of the literature and case series","volume":"52","author":"Coppit","year":"2000","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"81","DOI":"10.6004\/jnccn.2020.0001","article-title":"Pediatric Acute Lymphoblastic Leukemia, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology","volume":"18","author":"Brown","year":"2020","journal-title":"J. Natl. Compr. Cancer Netw. JNCCN"},{"key":"ref_19","first-page":"23","article-title":"Topics in pediatric leukemia\u2014Acute lymphoblastic leukemia","volume":"7","author":"Esparza","year":"2005","journal-title":"MedGenMed Medscape Gen. Med."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Bernt, K.M., and Hunger, S.P. (2014). Current concepts in pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia. Front. Oncol., 4.","DOI":"10.3389\/fonc.2014.00054"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA A Cancer J. Clin."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/1746-160X-5-22","article-title":"The nature of fibrous dysplasia","volume":"5","author":"Feller","year":"2009","journal-title":"Head. Face Med."},{"key":"ref_23","first-page":"4132842","article-title":"Mesenchymal Hamartoma in Children: A Diagnostic Challenge","volume":"2019","author":"Khan","year":"2019","journal-title":"Case Rep. Pediatr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.3892\/ol.2013.1584","article-title":"Solitary infantile myofibromatosis in the bones of the upper extremities: Two rare cases and a review of the literature","volume":"6","author":"Wu","year":"2013","journal-title":"Oncol. Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.jaad.2014.03.035","article-title":"Infantile myofibromatosis: A series of 28 cases","volume":"71","author":"Mashiah","year":"2014","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.jormas.2017.11.018","article-title":"Agressive pediatric myofibromatosis in a two-year-old child","volume":"119","author":"Letelier","year":"2018","journal-title":"J. Stomatol. Oral Maxillofac. Surg."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1590\/abd1806-4841.20175001","article-title":"Infantile myofibromatosis","volume":"92","author":"Larralde","year":"2017","journal-title":"An. Bras. Dermatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1136\/adc.2006.094706","article-title":"The investigation and management of chronic neutropenia in children","volume":"91","author":"James","year":"2006","journal-title":"Arch. Dis. Child."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1111\/bjh.14677","article-title":"How I manage children with neutropenia","volume":"178","author":"Dale","year":"2017","journal-title":"Br. J. Haematol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1002\/ajh.21616","article-title":"The incidence of immune thrombocytopenic purpura in children and adults: A critical review of published reports","volume":"85","author":"Terrell","year":"2010","journal-title":"Am. J. Hematol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Munir, F., Hardit, V., Sheikh, I.N., AlQahtani, S., He, J., Cuglievan, B., Hosing, C., Tewari, P., and Khazal, S. (2023). Classical Hodgkin Lymphoma: From Past to Future-A Comprehensive Review of Pathophysiology and Therapeutic Advances. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241210095"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1556\/OH.2014.29918","article-title":"Importance of the National Childhood Cancer Registry in the field of paediatric oncology care in Hungary","volume":"155","author":"Garami","year":"2014","journal-title":"Orv. Hetil."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1111\/bjh.15207","article-title":"A new approach to the treatment of acute myeloid leukaemia targeting the receptor for growth hormone-releasing hormone","volume":"181","author":"Jimenez","year":"2018","journal-title":"Br. J. Haematol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"315","DOI":"10.3322\/caac.21665","article-title":"Recent progress in the treatment of cancer in children","volume":"71","author":"Butler","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1007\/s12672-023-00658-7","article-title":"Modern treatment strategies in pediatric oncology and hematology","volume":"14","author":"Mikosza","year":"2023","journal-title":"Discov. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e2023061539","DOI":"10.1542\/peds.2023-061539","article-title":"Innovations in Cancer Treatment of Children","volume":"152","author":"Helms","year":"2023","journal-title":"Pediatrics"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/16\/8831\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:36:15Z","timestamp":1760110575000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/16\/8831"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,14]]},"references-count":36,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["ijms25168831"],"URL":"https:\/\/doi.org\/10.3390\/ijms25168831","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2024,8,14]]}}}