title: Growth Hormone Protects the Intestine Preserving Radiotherapy Efficacy on Tumors: A Short-Term Study.
abstract: The efficacy of radiotherapy on tumors is hampered by its devastating adverse effects on healthy tissue, particularly that of the gastrointestinal tract. These effects cause acute symptoms that are so disruptive to patients that they can lead to interruption of the radiotherapy program. These adverse effects could limit the intensity of radiation received by the patient, resulting in a sublethal dose to the tumor, thus increasing the risk of tumor resistance. The lack of an effective treatment to protect the bowel during radiation therapy to allow higher radiation doses that are lethal to the tumor has become a barrier to implementing effective therapy. In this study, we present a comparative analysis of both intestinal and tumor tissue in regard to the efficacy and the preventive impact of a short-term growth hormone (GH) treatment in tumor-bearing rats as a protective agent during radiotherapy. Our data show that the exogenous administration of GH improved intestinal recovery after radiation treatment while preserving the therapeutic effect against the tumor. GH significantly increased proliferation in the irradiated intestine but not in the irradiated tumors, as assessed by Positron Emission Tomography and the proliferative markers Ki67, cyclin D3, and Proliferating Cell Nuclear Antigen. This proliferative effect was consistent with a significant increase in irradiated intestinal villi and crypt length. Furthermore, GH significantly decreased caspase-3 activity in the intestine, whereas GH did not produce this effect in the irradiated tumors. In conclusion, short-term GH treatment protects the bowel, inducing proliferation while reducing apoptosis in healthy intestinal tissue and preserving radiotherapy efficacy on tumors.
authors.affiliation: Experimental Surgery Department, La Paz Hospital Research Institute, Madrid, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Caz
authors.affiliation: Experimental Surgery Department, La Paz Hospital Research Institute, Madrid, Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: Elvira
authors.affiliation: Experimental Surgery Department, La Paz Hospital Research Institute, Madrid, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Tabernero
authors.affiliation: Department of Radiation Oncology, La Paz University Hospital, Madrid, Spain.
authors.forename: Antonio G
authors.initials: AG
authors.lastname: Grande
authors.affiliation: Department of Nutrition, La Paz Hospital Research Institute, Madrid, Spain.
authors.forename: Bricia
authors.initials: B
authors.lastname: Lopez-Plaza
authors.affiliation: Experimental Surgery Department, La Paz Hospital Research Institute, Madrid, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: de Miguel
authors.affiliation: Experimental Surgery Department, La Paz Hospital Research Institute, Madrid, Spain.
authors.forename: Carlota
authors.initials: C
authors.lastname: Largo
authors.affiliation: Experimental Surgery Department, La Paz Hospital Research Institute, Madrid, Spain.
authors.forename: Monica
authors.initials: M
authors.lastname: Santamaria
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D013006:Growth Hormone / Q000494:pharmacology*; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000187:drug effects / Q000528:radiation effects; D007422:Intestines / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000528:radiation effects; D009369:Neoplasms / Q000532:radiotherapy*; D049268:Positron-Emission Tomography; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D011986:Receptors, Somatotropin / Q000378:metabolism; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D020011:Protective Agents; D011986:Receptors, Somatotropin; D019788:Fluorodeoxyglucose F18; D013006:Growth Hormone; D053148:Caspase 3